Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements.
A bile salt formed in the liver from chenodeoxycholate and glycine, usually as the sodium salt. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is a cholagogue and choleretic.
The formation of a solid in a solution as a result of a chemical reaction or the aggregation of soluble substances into complexes large enough to fall out of solution.
Databases devoted to knowledge about specific chemicals.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.
A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.
Potassium channels whose activation is dependent on intracellular calcium concentrations.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
The regulatory subunits of large-conductance calcium-activated potassium channels.
A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.
Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.
A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.
A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)
Behaviors associated with the ingesting of alcoholic beverages, including social drinking.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A specialty concerned with the study of anesthetics and anesthesia.
A publication issued at stated, more or less regular, intervals.
A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.
A dental specialty concerned with the prevention and correction of dental and oral anomalies (malocclusion).
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
Health care professionals, technicians, and assistants staffing LABORATORIES in research or health care facilities.
Chemicals necessary to perform experimental and/or investigative procedures and for the preparation of drugs and other chemicals.

Cloning and characterization of the promoters of the maxiK channel alpha and beta subunits. (1/827)

Large conductance, calcium-activated potassium (maxiK) channels are expressed in nerve, muscle, and other cell types and are important determinants of smooth muscle tone. To determine the mechanisms involved in the transcriptional regulation of maxiK channels, we characterized the promoter regions of the pore forming (alpha) and regulatory (beta) subunits of the human channel complex. Maximum promoter activity (up to 12.3-fold over control) occurred between nucleotides -567 and -220 for the alpha subunit (hSlo) gene. The minimal promoter is GC-rich with 5 Sp-1 binding sites and several TCC repeats. Other transcription factor-binding motifs, including c/EBP, NF-kB, PU.1, PEA-3, Myo-D, and E2A, were observed in the 5'-flanking sequence. Additionally, a CCTCCC sequence, which increases the transcriptional activity of the SM1/2 gene in smooth muscle, is located 27 bp upstream of the TATA-like sequence, a location identical to that found in the SM1/2 5'-flanking region. However, the promoter directed equivalent expression when transfected into smooth muscle and other cell types. Analysis of the hSlo beta subunit 5'-flanking region revealed a TATA box at position -77 and maximum promoter activity (up to 11.0-fold) in a 200 bp region upstream from the cap site. Binding sites for GATA-1, Myo-D, c-myb, Ets-1/Elk-1, Ap-1, and Ik-2 were identified within this sequence. Two CCTCCC elements are present in the hSlo beta subunit promoter, but tissue-specific transcriptional activity was not observed. The lack of tissue-specific promoter activity, particularly the finding of promoter activity in cells from tissues in which the maxiK gene is not expressed, suggests a complex channel regulatory mechanism for hSlo genes. Moreover, the lack of similarity of the promoters of the two genes suggests that regulation of coordinate expression of the subunits does not occur through equivalent cis-acting sequences.  (+info)

RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels. (2/827)

Large-conductance Ca2+- and voltage-activated BK-type K+ channels are expressed abundantly in normal rat pancreatic islet cells and in the clonal rat insulinoma tumor (RINm5f) and hamster insulinoma tumor (HIT) beta cell lines. Previous work has suggested that the Ca2+ sensitivity of BK channels in RIN cells is substantially less than that in HIT cells, perhaps contributing to differences between the cell lines in responsiveness to glucose in mediating insulin secretion. In both RIN cells and normal pancreatic beta cells, BK channels are thought to play a limited role in responses of beta cells to secretagogues and in the electrical activity of beta cells. Here we examine in detail the properties of BK channels in RIN and HIT cells using inside-out patches and whole cell recordings. BK channels in RIN cells exhibit rapid inactivation that results in an anomalous steady-state Ca2+ dependence of activation. In contrast, BK channels in HIT cells exhibit the more usual noninactivating behavior. When BK inactivation is taken into account, the Ca2+ and voltage dependence of activation of BK channels in RIN and HIT cells is essentially indistinguishable. The properties of BK channel inactivation in RIN cells are similar to those of inactivating BK channels (termed BKi channels) previously identified in rat chromaffin cells. Inactivation involves multiple, trypsin-sensitive cytosolic domains and exhibits a dependence on Ca2+ and voltage that appears to arise from coupling to channel activation. In addition, the rates of inactivation onset and recovery are similar to that of BKi channels in chromaffin cells. The charybdotoxin (CTX) sensitivity of BKi currents is somewhat less than that of the noninactivating BK variant. Action potential voltage-clamp waveforms indicate that BK current is activated only weakly by Ca2+ influx in RIN cells but more strongly activated in HIT cells even when Ca2+ current magnitude is comparable. Concentrations of CTX sufficient to block BKi current in RIN cells have no effect on action potential activity initiated by glucose or DC injection. Despite its abundant expression in RIN cells, BKi current appears to play little role in action potential activity initiated by glucose or DC injection in RIN cells, but BK current may play an important role in action potential repolarization in HIT cells.  (+info)

The beta subunit increases the Ca2+ sensitivity of large conductance Ca2+-activated potassium channels by retaining the gating in the bursting states. (3/827)

Coexpression of the beta subunit (KV,Cabeta) with the alpha subunit of mammalian large conductance Ca2+- activated K+ (BK) channels greatly increases the apparent Ca2+ sensitivity of the channel. Using single-channel analysis to investigate the mechanism for this increase, we found that the beta subunit increased open probability (Po) by increasing burst duration 20-100-fold, while having little effect on the durations of the gaps (closed intervals) between bursts or on the numbers of detected open and closed states entered during gating. The effect of the beta subunit was not equivalent to raising intracellular Ca2+ in the absence of the beta subunit, suggesting that the beta subunit does not act by increasing all the Ca2+ binding rates proportionally. The beta subunit also inhibited transitions to subconductance levels. It is the retention of the BK channel in the bursting states by the beta subunit that increases the apparent Ca2+ sensitivity of the channel. In the presence of the beta subunit, each burst of openings is greatly amplified in duration through increases in both the numbers of openings per burst and in the mean open times. Native BK channels from cultured rat skeletal muscle were found to have bursting kinetics similar to channels expressed from alpha subunits alone.  (+info)

ATP inhibition of a mouse brain large-conductance K+ (mslo) channel variant by a mechanism independent of protein phosphorylation. (4/827)

1. We investigated the effect of ATP in the regulation of two closely related cloned mouse brain large conductance calcium- and voltage-activated potassium (BK) channel alpha-subunit variants, expressed in human embryonic kidney (HEK 293) cells, using the excised inside-out configuration of the patch-clamp technique. 2. The mB2 BK channel alpha-subunit variant expressed alone was potently inhibited by application of ATP to the intracellular surface of the patch with an IC50 of 30 microM. The effect of ATP was largely independent of protein phosphorylation events as the effect of ATP was mimicked by the non-hydrolysable analogue 5'-adenylylimidodiphosphate (AMP-PNP) and the inhibitory effect of ATPgammaS was reversible. 3. In contrast, under identical conditions, direct nucleotide inhibition was not observed in the closely related mouse brain BK channel alpha-subunit variant mbr5. Furthermore, direct nucleotide regulation was not observed when mB2 was functionally coupled to regulatory beta-subunits. 4. These data suggest that the mB2 alpha-subunit splice variant could provide a dynamic link between cellular metabolism and cell excitability.  (+info)

Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog. (5/827)

Voltage-dependent and calcium-sensitive K+ (MaxiK) channels are key regulators of neuronal excitability, secretion, and vascular tone because of their ability to sense transmembrane voltage and intracellular Ca2+. In most tissues, their stimulation results in a noninactivating hyperpolarizing K+ current that reduces excitability. In addition to noninactivating MaxiK currents, an inactivating MaxiK channel phenotype is found in cells like chromaffin cells and hippocampal neurons. The molecular determinants underlying inactivating MaxiK channels remain unknown. Herein, we report a transmembrane beta subunit (beta2) that yields inactivating MaxiK currents on coexpression with the pore-forming alpha subunit of MaxiK channels. Intracellular application of trypsin as well as deletion of 19 N-terminal amino acids of the beta2 subunit abolished inactivation of the alpha subunit. Conversely, fusion of these N-terminal amino acids to the noninactivating smooth muscle beta1 subunit leads to an inactivating phenotype of MaxiK channels. Furthermore, addition of a synthetic N-terminal peptide of the beta2 subunit causes inactivation of the MaxiK channel alpha subunit by occluding its K+-conducting pore resembling the inactivation caused by the "ball" peptide in voltage-dependent K+ channels. Thus, the inactivating phenotype of MaxiK channels in native tissues can result from the association with different beta subunits.  (+info)

Cyclic GMP-dependent protein kinase activates cloned BKCa channels expressed in mammalian cells by direct phosphorylation at serine 1072. (6/827)

NO-induced activation of cGMP-dependent protein kinase (PKG) increases the open probability of large conductance Ca2+-activated K+ channels and results in smooth muscle relaxation. However, the molecular mechanism of channel regulation by the NO-PKG pathway has not been determined on cloned channels. The present study was designed to clarify PKG-mediated modulation of channels at the molecular level. The cDNA encoding the alpha-subunit of the large conductance Ca2+-activated K+ channel, cslo-alpha, was expressed in HEK293 cells. Whole cell and single channel characteristics of cslo-alpha exhibited functional features of native large conductance Ca2+-activated K+ channels in smooth muscle cells. The NO-donor sodium nitroprusside increased outward current 2.3-fold in whole cell recordings. In cell-attached patches, sodium nitroprusside increased the channel open probability (NPo) of cslo-alpha channels 3.3-fold without affecting unitary conductance. The stimulatory effect of sodium nitroprusside was inhibited by the PKG-inhibitor KT5823. Direct application of PKG-Ialpha to the cytosolic surface of inside-out patches increased NPo 3.2-fold only in the presence of ATP and cGMP without affecting unitary conductance. A point mutation of cslo-alpha in which Ser-1072 (the only optimal consensus sequence for PKG phosphorylation) was replaced by Ala abolished the PKG effect on NPo in inside-out patches and the effect of SNP in cell attached patches. These results indicate that PKG activates cslo-alpha by direct phosphorylation at serine 1072.  (+info)

Glucocorticoid block of protein kinase C signalling in mouse pituitary corticotroph AtT20 D16:16 cells. (7/827)

1. The regulation of large conductance calcium- and voltage-activated potassium (BK) currents by activation of the protein kinase C (PKC) and glucocorticoid signalling pathways was investigated in AtT20 D16:16 clonal mouse anterior pituitary corticotroph cells. 2. Maximal activation of PKC using the phorbol esters, 4beta-phorbol 12-myristate, 13-acetate (PMA), phorbol 12, 13 dibutyrate (PDBu) and 12-deoxyphorbol 13-phenylacetate (dPPA) elicited a rapid, and sustained, inhibition of the outward steady-state voltage- and calcium- dependent potassium current predominantly carried through BK channels. 3. The effect of PMA was blocked by the PKC inhibitors bisindolylmaleimide I (BIS; 100 nM) and chelerythrine chloride (CHE; 25 microM) and was not mimicked by the inactive phorbol ester analogue 4alpha-PMA. 4. PMA had no significant effect on the 1 mM tetraethylammonium (TEA)-insensitive outward current or pharmacologically isolated, high voltage-activated calcium current. 5. PMA had no significant effect on steady-state outward current in cells pre-treated for 2 h with 1 microM of the glucocorticoid agonist dexamethasone. Dexamethasone had no significant effect on steady-state outward current amplitude or sensitivity to 1 mM TEA and did not block PMA-induced translocation of the phorbol ester-sensitive PKC isoforms, PKCalpha and PKCepsilon, to membrane fractions. 6. Taken together these data suggest that in AtT20 D16:16 corticotroph cells BK channels are important targets for PKC action and that glucocorticoids inhibit PKC signalling downstream of PKC activation.  (+info)

Simultaneous binding of two protein kinases to a calcium-dependent potassium channel. (8/827)

Large-conductance calcium-dependent potassium channels are subject to modulation by protein kinases, phosphatases, and other signaling proteins, and it has been inferred from electrophysiological experiments that signaling proteins sometimes can be intimately associated with these channels in a regulatory complex. We show here that endogenous protein kinase activity coimmunoprecipitates with both native and recombinant Drosophila Slowpoke (dSlo) calcium-dependent potassium channels. Coimmunoprecipitation experiments using antibodies against several protein kinases demonstrate that dSlo can bind simultaneously to the Src tyrosine kinase and to the catalytic subunit of the cAMP-dependent protein kinase (PKAc). Both kinases can phosphorylate the channel in Drosophila heads and in heterologous host cells. The PKAc binds directly to a 172-amino acid region in the C-terminal domain of dSlo, without the intervention of regulatory subunits or anchoring proteins, and channel phosphorylation by PKAc is not required for this binding interaction. In contrast, several phosphorylatable tyrosine residues in dSlo are important for Src binding. The results are consistent with the idea that an ion channel can act as a scaffold for its own specific set of modulatory enzymes.  (+info)

Resveratrol has been reported to stimulate BKCa currents in human vascular endothelial cells and human cardiac fibroblasts [24, 51], which might be associated with its cardioprotective effect. The present study demonstrated that resveratrol could stimulate the activities of BKCa channels in cortical neurons. In fact, BKCa channel is considered to be one of the intrinsic molecular determinants for the control of neuronal excitability in the central nervous system and play a role in the etiology of some neurological diseases. Recent studies have demonstrated the implication of BKCa channels in Fragile X Syndrome (FXS) pathology [22]. In fact, a selective BKCa channel opener molecule (BMS-204352) rescues a broad spectrum of behavioral impairments (social, emotional and cognitive) in an animal model of FXS [17]. Resveratrol might be also beneficial to patients with FXS.. BKCa channels also play an important role in seizure etiology. Loss-of-function BKCa channel mutations can lead to temporal lobe ...
There is ample evidence that ion channel modulation by accessory proteins within a macromolecular complex can regulate channel activity and thereby impact neuronal excitability. However, the downstream consequences of ion channel modulation remain largely undetermined. The Drosophila melanogaster large conductance calcium-activated potassium channel SLOWPOKE (SLO) undergoes modulation via its binding partner SLO-binding protein (SLOB). Regulation of SLO by SLOB influences the voltage dependence of SLO activation and modulates synaptic transmission. SLO and SLOB are expressed especially prominently in median neurosecretory cells (mNSCs) in the pars intercerebralis (PI) region of the brain; these cells also express and secrete Drosophila insulin like peptides (dILPs). Previously, we found that flies lacking SLOB exhibit increased resistance to starvation, and we reasoned that SLOB may regulate aspects of insulin signaling and metabolism. Here we investigate the role of SLOB in metabolism and find that
The properties of single Ca2+-activated K+ (BK) channels in neonatal rat intracardiac neurons were investigated using the patch-clamp recording technique. In symmetrical 140 mM K+. the single-channel slope conductance was linear in the voltage range -60/+60 mV, and was 207±19 pS. Na+ ions were not measurably permeant through the open channel. Channel activity increased with the cytoplasmic free Ca2+ concentration ([Ca2+]i) with a Hill plot giving a half-saturating [Ca2+] (K0.5) of 1.35 μM and slope of ≅3. The BK channel was inhibited reversibly by external tetraethylammonium (TEA) ions, charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and apamin. Ionomycin (1-10 μM) increased BK channel activity in the cell-attached recording configuration. The resting activity was consistent with a [Ca2+]i |100 nM and the increased channel activity evoked by ionomycin was consistent with a rise in|[Ca2+]i to ≥ 0.3 μM. TEA (0.2-1 mM) increased the action potential duration 1.5-fold and
Overactive bladder (OAB) is mostly observed in obese individuals, and is associated with enhanced excitability and contractility of the detrusor smooth muscle (DSM). Large-conductance voltage- and Ca2+-activated K+ (BK) channels reduce the excitability and contractility of the DSM. We tested whether obesity-induced OAB is associated with altered BK channel expression and activity in the DSM. Seven-week-old female Sprague-Dawley rats (N=80) were fed a normal or high-fat diet (HFD) for 12 weeks. HFD-fed rats exhibited a higher average bodyweight and urodynamically established detrusor overactivity. mRNA levels of the Kcnma1 (BKα subunit) and Kcnmb1 (BKβ1 subunit) in whole tissues and cells from the DSM were reduced in HFD-fed rats. A selective BK channel opener, NS1619, was then applied to DSM cells from the two groups of rats. Patch-clamp techniques revealed that spontaneous transient outward currents, NS1619-induced activation of spontaneous transient
Fig. 2 B), consistent with negative cooperativity between sites in the same subunit (Sweet and Cox, 2008). In contrast, another group performing similar experiments at +50 mV concluded that positive cooperativity exists between the two binding sites (Qian et al., 2006). In the latter case, positive cooperativity could potentially be accounted for if both Ca2+ sites were coupled to the voltage sensor because the voltage sensor is not held in a resting state at +50 mV. However Sweet and Cox (2008) concluded that the RCK1 site is solely responsible for Ca2+-sensor/voltage-sensor coupling. A recent study combining Ca2+ site mutations and voltage clamp fluorometry to monitor the effects of Ca2+ on steady-state voltage-sensor activation and Po reached conclusions similar to that of Sweet and Cox (2008) regarding intrasubunit cooperativity and Ca2+-sensor/voltage-sensor coupling (Savalli et al., 2012). However, this study also suggested that Ca2+ site mutations may have effects other than elimination ...
Characterisation and interaction between β₂ adrenoceptor (AR) and the large conductance calcium-activated potassium (BK_C_a) channel in human myometrium during pregnancy ...
Large-conductance calcium-activated (maxi-K, BK) potassium channels are widely distributed in the brain. Maxi-K channels function as neuronal calcium sensors and contribute to the control of cellular excitability and the regulation of neurotransmitter release. Little is currently known of any significant role of maxi-K channels in the genesis of neurological disease. Recent advances in the molecular biology and pharmacology of these channels have revealed sources of phenotypic variability and demonstrated that they can be successfully modulated by pharmacological agents. A potential role is suggested in the treatment of conditions such as ischemic stroke and cognitive disorders ...
Spider venoms are actively being investigated as sources of novel insecticidal agents for biopesticide engineering. After screening 37 theraphosid spider venoms, a family of three new short-loop inhibitory cystine knot insecticidal toxins (kappa-TRTX-Ec2a, kappa-TRTX-Ec2b, and kappa-TRTX-Ec2c) were isolated and characterized from the venom of the African tarantula Eucratoscelus constrictus. Whole-cell patch-clamp recordings from cockroach dorsal unpaired median neurons revealed that, despite significant sequence homology with other theraphosid toxins, these 29-residue peptides lacked activity on insect voltage-activated sodium and calcium channels. It is noteworthy that kappa-TRTX-Ec2 toxins were all found to be high-affinity blockers of insect large-conductance calcium-activated K+ (BKCa) channel currents with IC50 values of 3 to 25 nM. In addition, kappa-TRTX-Ec2a caused the inhibition of insect delayed-rectifier K+ currents, but only at significantly higher concentrations. kappa-TRTX-Ec2a ...
anti-Potassium Large Conductance Calcium-Activated Channel, Subfamily M, beta Member 1 (KCNMB1) antibody (Alexa Fluor 647) ABIN903516 from antibodies-online
J:102457 Chen L, Tian L, MacDonald SH, McClafferty H, Hammond MS, Huibant JM, Ruth P, Knaus HG, Shipston MJ, Functionally diverse complement of large conductance calcium- and voltage-activated potassium channel (BK) alpha-subunits generated from a single site of splicing. J Biol Chem. 2005 Sep 30;280(39):33599-609 ...
Drosophila SLOWPOKE (SLO) is a voltage and calcium dependent, large conductance potassium channel important for action potential repolarization, neuronal excitability, neurotransmitter release, and hormone secretion. SLO binding protein (SLOB) binds to and modulates SLO activity. We have shown previously that modulation of SLO by SLOB has profound effects on SLO channel currents, synaptic transmisison, and metabolism. Multiple isoforms of SLOB exist and are encoded by multiple transcripts; the isoforms are named based on their predicted protein molecular weights, in kilodaltons. In the Drosophila brain, SLOB57/51 proteins are expressed especially prominently in insulin producing neurons of the pars intercerebralis, while SLOB71/65 proteins are enriched in the lateral neurons that participate in the generation of circadian rhythms. Here we sought to determine the transcription initiation sites in the slob gene and investigated promoter elements responsible for expression of the different slob
Calcium-activated potassium channel subunit alpha-1, Potassium Calcium-Activated Channel Subfamily M Alpha 1 or Slo1/BKalpha is encoded by the gene KCNMA1. BKalpha binds to one of 4 different beta subunits to form a channel in the calcium activated large conductance (MaxiK channel) family. This potassium channel is activated by membrane depolarization or an increase in cytosolic ca2+ and mediated the export of K+. BKalpha is involved with various cell processes including contraction of smooth muscle, regulation of transmitter release, innate immunity and regulation of membrane potential. Diseases associated with KCNMA1 include forms of Epilepsy and Developmental Delay Cerebellar Atrophy and Seizures.. ...
The large conductance calcium- and voltage-activated K+ channel (KCa1.1, BK, MaxiK) is ubiquitously expressed in the body, and holds the ability to integrate changes in intracellular calcium and membrane potential. This makes the BK channel an important negative feedback system linking increases in intracellular calcium to outward hyperpolarizing potassium currents. Consequently, the channel has many important physiological roles including regulation of smooth muscle tone, neurotransmitter release and neuronal excitability. Additionally, cardioprotective roles have been revealed in recent years. After a short introduction to the structure, function and regulation of BK channels, we review the small organic molecules activating BK channels and how these tool compounds have helped delineate the roles of BK channels in health and disease.
Then there are the big conductance channels BKCa is a potassium channel that opens in response to high internal concentrations of calcium (highly positive) or when the membrane of the cell is highly depolarised (highly positive). This causes potassium to flood out of the cell making the inside of the cell less positive, it resets the nerve allowing it to fire again, unless it makes the inside of the cell very less positive, it can stop nerves firing again and it stops damage. ...
Electrical tuning is a phenomenon by which certain vertebrates discriminate between different frequencies of sound. Electrical resonance results when the inherent oscillation in the membrane potential of hair cells corresponds to sound of a particular frequency. This gives rise to a resonance and amplification of signal with consequent transmitter release from these cells.. The inherent oscillation in membrane potential in a hair cell is brought about by an inward Calcium current and an outward Potassium current (calcium dependent). The systematic variation in the frequency of such an oscillation in hair cells that occurs across the tonotopic axis is brought about primarily by a variation in the kinetic properties of the Potassium current. Previously we had shown that some of this variation in kinetic properties of this current was brought about by alternative splicing of this BK potassium channel. However, a large part of this variation in kinetics cannot be explained by alternative splicing ...
Liao, P., Yu, D., Li, G., Tan, F.Y., Tuck, W.S., Jia, L.S., Yeow, L.C. (2007). A smooth muscle Cav1.2 calcium channel splice variant underlies hyperpolarized window current and enhanced state-dependent inhibition by nifedipine. Journal of Biological Chemistry 282 (48) : 35133-35142. [email protected] Repository. https://doi.org/10.1074/jbc. ...
Recently, we reported that the activities of large conductance Ca2+-activated K+(BK) channels are inhibited by caveolae microdomain targeting in vascular endothelial cells. The molecular mechanism of this negative regulation of BK channels by caveolae is unknown. In this study, we tested the hypotheses that BK channels are inhibited by physical interaction with the scaffolding domain of caveolin-1, which alters the properties of the channel. Using HEK293 cells stably expressing hSlo (which encodes human BK channels) with and without transient transfection with caveolin-1, We found that hSlo channels were enriched in the low buoyant density fraction when co-expressed with caveolin-1 and the channels were co-immunoprecipitated by anti-caveolin-1 antibodies. Co-expression of caveolin-1 resulted in inhibition of whole-cell hSlo current densities from 77.0±18.0 pA/pF in control (HP=−60 mV, TP=+80 mV, 1 μM free Ca2+, n=10) to 12.0±3.9 pA/pF (n=8, p,0.01 vs. control). In contrast, co-expression of ...
BK channels are critical regulators of neuronal activity, controlling firing, neurotransmitter release, cerebellar function, and BK channel mutations have been linked to seizure disorders. Modulation of BK channel gating is well characterized, regulated by accessory subunit interactions, intracellular signaling pathways, and membrane potential. In contrast, the role of intracellular trafficking mechanisms in controlling BK channel function, especially in live cells, has been less studied. Fluorogen activating peptides (FAPs) are well-suited for trafficking and physiological studies due to the binding of malachite green (MG) based dyes with sub-nanomolar affinity to the FAP, resulting in bright, photostable, far-red fluorescence. Cell-excluded MG dyes enable the selective tagging of surface protein and tracking through endocytic pathways. We used CRISPR to insert the FAP at the extracellular N-terminus of BKα in the first exon of its native locus, enabling regulation by the native promoter elements and
Our previous study demonstrated that pregnancy increased large-conductance Ca2+-activated potassium channel β1 subunit (BKβ1) expression and large-conductance Ca2+-activated potassium channel activity in uterine arteries, which were abrogated by chronic hypoxia. The present study tested the hypothesis that promoter methylation/demethylation is a key mechanism in epigenetic reprogramming of BKβ1 expression patterns in uterine arteries. Ovine BKβ1 promoter of 2315 bp spanning from −2211 to +104 of the transcription start site was cloned, and an Sp1−380 binding site that contains CpG dinucleotide in its core binding sequences was identified. Site-directed deletion of the Sp1 site significantly decreased the BKβ1 promoter activity. Estrogen receptor-α bound to the Sp1 site through tethering to Sp1 and upregulated the expression of BKβ1. The Sp1 binding site at BKβ1 promoter was highly methylated in uterine arteries of nonpregnant sheep, and methylation inhibited transcription factor ...
View mouse Kcnmb4 Chr10:116417861-116473542 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
BK channels are composed of pore-forming α- and accessory β1-subunits.16,17 Increases in BK channel α-subunit expression and function occur in arteries from SHR and aldosterone-salt hypertensive rats18-24 suggesting that there is a dynamic relationship between blood pressure and BK channels.20,23 Pressure-induced upregulation of BK channel α-subunit protein levels and channel function in vasculature provides an important counterregulatory mechanism to prevent further increases in arterial tone. We found previously that tempol caused larger IBTX-sensitive vasodilations in DOCA-salt MA. In the present studies, IBTX-sensitive Io was larger in DOCA-salt myocytes, but there was no change in single-channel Po. These data indicate that BK channel expression might be increased in DOCA-salt MA. These functional data are consistent with Western blot and immunocytochemical data that show increased BK channel α-subunit expression in DOCA-salt MA.8 Based on the current and previously published work, we ...
Activation of Ca2+-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca2+ signals (Ca2+ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues. Oxidant-activated PKG was required to trigger Ca2+ sparks, BK channel activity, and vasodilation in response to pressure. VSMCs from arteries from mice expressing a form of PKG that could not be activated by oxidants showed reduced Ca2+ spark frequency, and arterial preparations from these mice had decreased pressure-induced activation of BK channels. Thus, the absence of oxidative activation of PKG disabled the BK channel-mediated negative feedback ...
Inhibition of native BK channel activity in aortic myocytes in response to a cholesterol-enrichment medium has been found coincidental with a decrease in the rotational diffusion coefficient of diphenylhexatriene, the latter being interpreted as a decrease in the fluidity of the cell membrane (Bolotina et al., 1989). On the other hand, Chang et al. (1995) reconstituted BK channels into binary phospholipid bilayers and determined from Arrhenius plots the activation energy for channel transitions from the open to the closed state(s). Cholesterol 11% (wt/wt) significantly reduced such energy, and thus, cholesterol-induced decrease in Po was interpreted to result, at least partially, from destabilization of the BK channel open state(s), likely reflected by a reduction in channel mean open time. The computed lateral elastic stress energy that resulted from cholesterol presence in the lipid mix was significantly higher than the BK activation energy from closed to open state(s), making it possible to ...
1. DDT1 MF-2 smooth muscle cells responded to the bath application of histamine or ATP with an increase in the cytosolic Ca2+ concentration ([Ca2+]c) and the whole-cell K+ current, IK(BA). 2. In cell-attached patches, histamine (100 microM) activated currents through a 200 pS K+ channel (BKA channel). In the absence of agonists, the BKA channel was activated by excision of the patch. Both histamine and patch excision increased the channel activity (NPo; where N is the number of channels per patch and Po is the open probability) by reducing the long closures between the bursts of openings. 3. In inside-out patches, the BKA channel had a conductance of 201 +/- 4 pS (symmetrical solutions of 150 mM KCl, 2 mM MgCl2 and 2 mM EGTA). Replacement of K+ in the patch electrode by Na+, Li+ or Cs+ prevented the flow of inward currents and reduced the outward K+ conductance to 113 pS. 4. NPo was insensitive to changes in [Ca2+]c from 10 nM to 1 microM. NPo was also not modified either by cytosolic Na+, ATP, GTP,
Data Availability StatementAll relevant data are within the paper. generate outward potassium currents that bring the membrane potential back to resting levels and oppose vasoconstriction [2C4]. In vascular clean muscle, BK channels have been reported to consist of a pore-forming alpha subunit and two types of accessory subunits: beta1 protein (BK beta1 subunit) and leucine-rich repeat containing protein 26 (BK gamma subunit) [1, 5C6]. Accessory proteins cannot form functional channels, but enable BK channel activation at lower transmembrane voltages when compared to homomeric channels created by BK alpha subunit tetramers [7C8]. BK beta 1 subunits also improve the channels pharmacological profile by conferring, enhancing, or diminishing level of sensitivity to several endogenous and synthetic chemical regulators [9C13]. BK channels remain a constant focus of drug finding, including BK focusing on by newly developed compounds that modulate cerebral artery diameter and could potentially mitigate ...
Kun, Attila (2013) A MAGAS KONDUKTANCIÁJÚ CA2+ AKTIVÁLTA K+ CSATORNÁK BEFOLYÁSOLÁSA A DIABETESES ÉRSZÖVŐDMÉNYEK KEZELÉSÉRE = MODULATION OF LARGE-CONDUCTANCE CALCIUM-ACTIVATED K+ CHANNELS TO TREAT DIABETIC VASCULAR DYSFUNCTION. Project Report. OTKA. Varró, András and Acsai, Károly and Baczkó, István and Biliczki, Péter and Bitay, Miklós and Farkas, Attila and Farkas, András and Hála, Ottó and Jost, Norbert László and Koncz, István and Kormányos, Zsolt and Kovács, Mária and Krassói, Irén and Kun, Attila and Lengyel, Csaba Attila and Leprán, István and Márton, Zoltán and Nagy, Zsolt Ákos and Ördög, Balázs and Papp, Gyula and Papp, Rita and Pataricza, János and Prandovszky, Emese and Prorok, János and Sághy, László and Szuts, Viktória and Tóth, András and Vajda, Szilvia and Ványi, József and Végh, Ágnes and Virág, László (2009) A szívritmuszavarok és a myocardiális repolarizáció mechanizmusainak vizsgálata; antiaritmiás és proaritmiás ...
The high-conductance Ca(2+)-activated K channel (BK channel) is not only regulated by a number of physiological stimuli, but it is also sensitive to pharmacological modulation. We have stably expressed the alpha-subunit of the human BK channel, hslo, in HEK 293 cells and studied by patch-clamp techn …
KCNMB2 antibody (potassium large conductance calcium-activated channel, subfamily M, beta member 2) for IHC, WB. Anti-KCNMB2 pAb (GTX16645) is tested in Human, Rat samples. 100% Ab-Assurance.
Methods, devices, and systems for monitoring a number of recurrent activities of an individual are disclosed. One method for monitoring a recurrent activity of an individual using activity windowing includes recording a number of sensor activations of at least one sensor, determining a number of peaks in the number of sensor activations, defining one or more time frames based upon the location of at least one of the number of peaks in the time period, and applying a rule associated with a threshold number of activations, where the rule is applied to at least one particular time frame in order to determine whether to initiate an action.
As MVNOs become more common, consolidation will occur, often through the network owners buying up their virtual rivals. This can be a powerful tactic for a major cellco - letting an MVNO use its brand strength to attract a customer base, perhaps in a market that the network owner had failed to penetrate; commanding leasing fees for the network in the meantime; and then acquiring it once the user base has been built. In Finland, Elisa is looking to buy MVNO Saunalahti, while TeliaSonera of Sweden and Finland is to acquire two Norwegian virtual operators, Sense and Chess. Scandinavia, which was a pioneer of the MVNO model, is also a good indicator of trends that will start to affect other territories where the concept is less established.. For instance, the history of MVNO acquisitions in Scandinavia indicates the rising value of these companies. When TDC of Denmark bought Telmore in January 2004 it paid €88 per subscriber, while Elisa will pay €680 per sub and TeliaSonera €563, in markets ...
Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat coronary artery smooth muscle cells.: D
Large-conductance calcium and voltage-activated potassium channels, termed SLO-1 (or BK), are pivotal players in the regulation of cell excitability across the animal phyla. Furthermore, emerging evidence indicates that these channels are key mediators of a number of neuroactive drugs, including the most recent new anthelmintic, the cyclo-octadepsipeptide emodepside. Detailed reviews of the structure, function and pharmacology of BK channels have recently been provided (Salkoff et al. in Nat Rev Neurosci 7:921-931, 2006; Ghatta et al. in Pharmacol Ther 110:103-116, 2006) and therefore these aspects will only briefly be covered here. The purpose of this review is to discuss how SLO-1 channels might function as regulators of neural transmission and network activity. In particular, we focus on the role of SLO-1 in the regulation of Caenorhabditis elegans behaviour and highlight the role of this channel as an effector for pleiotropic actions of neuroactive drugs, including emodepside. On the premise ...
Quinethazone is only found in individuals that have used or taken this drug. It is a thiazide diuretic used to treat hypertension. Common side effects include dizziness, dry mouth, nausea, and low potassium levels.As a diuretic, quinethazone inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like quinethazone also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of quinethazone is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle ...
article{1b02e879-41a5-4cd0-99a2-8efc8c0a4125, abstract = {Voltage-activated potassium channels (Kv channels) in the microvillar photoreceptors of arthropods are responsible for repolarization and regulation of photoreceptor signaling bandwidth. On the basis of analyzing Kv channels in dipteran flies, it was suggested that diurnal, rapidly flying insects predominantly express sustained K+ conductances, whereas crepuscular and nocturnally active animals exhibit strongly inactivating Kv conductances. The latter was suggested to function for minimizing cellular energy consumption. In this study we further explore the evolutionary adaptations of the photoreceptor channelome to visual ecology and behavior by comparing K+ conductances in 15 phylogenetically diverse insects, using patch-clamp recordings from dissociated ommatidia. We show that rapid diurnal flyers such as the blowfly (Calliphora vicina) and the honeybee (Apis mellifera) express relatively large noninactivating Kv conductances, ...
The activation of large conductance Ca2+-activated K+ (BK) channels results in cellular hyperpolarization and decreased excitation. Protein kinase C (PKC), adenosine 3′,5′-monophosphate (cAMP)-dependent protein kinase (PKA), and guanosine 3′,5′-monophosphate (cGMP)-dependent protein kinase (PKG) regulate the activity of BK channels. However, the mechanism by which these kinases regulate BK channel activity remains largely unknown. Zhou et al. cloned three isoforms of the BK channel α subunit, which differ only in their COOH-termini: both the A (BKA) and B (BKB) isoforms have two serine residues that serve as sites for protein kinase C (PKC)-mediated phosphorylation, whereas the C (BKC) isoform does not. Inside-out cell membrane patches from HEK293 cells that expressed BKA or BKB were activated by the application of PKG but not by PKA, whereas BKC-containing inside-out patches were only activated by the application of PKA. Upon mutation of the PKC-mediated phosphorylation sites (serine ...
TY - JOUR. T1 - Erratum. T2 - Wanderlust kinetics and variable Ca2+-sensitivity of dSlo, a large conductance Ca2+-activated K+ channel, expressed in oocytes (Biophysical Journal (1996) 70 (2640-2651)). AU - Silberberg, S. D.. AU - Lagrutta, A.. AU - Adelman, J. P.. AU - Magleby, K. L.. PY - 1996/1/1. Y1 - 1996/1/1. UR - http://www.scopus.com/inward/record.url?scp=0030006619&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0030006619&partnerID=8YFLogxK. M3 - Comment/debate. AN - SCOPUS:0030006619. VL - 71. JO - Biophysical Journal. JF - Biophysical Journal. SN - 0006-3495. IS - 1. ER - ...
BK channels regulate vascular tone by hyperpolarizing smooth muscle in response to fluctuating calcium concentrations. Oestrogen has been reported to lower blood pressure by increasing BK channel open probability through direct binding to the regulatory beta1-subunit(s) associated with the channel. The present investigation demonstrates that 17beta-oestradiol activates the BK channel complex by increasing the burst duration of channel openings. A subconductance state was observed in 25% of recordings following the addition of 17beta-oestradiol and could reflect uncoupling between the pore forming alpha1-subunit and the regulatory beta1-subunit. We also present evidence that more than one beta1-subunit is required to facilitate binding of 17beta-oestradiol to the channel complex.
Embodiments of the present invention relate to methods, devices, and systems to monitor activity. One method to monitor activity includes monitoring a sensor activated by an individual. The method also includes recording activation of the sensor, determining a behavior routine of the individual based on recorded activations of the sensor, and analyzing the recorded sensor activations to determine a behavior routine. The method also includes identifying a change in the behavior routine based on the analysis of the recorded sensor activations.
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Intracellular trafficking pathways that control surface expression of vascular myocyte ion channels are poorly understood. The aim of this study was to identify mechanism(s) and functional significance of BKα trafficking and to investigate regulation by vasoactive agents in arterial myocytes. Our data indicate that 1) BKα is primarily plasma membrane-localized and is trafficked to the plasma membrane via a rab4A-dependent, but not rab11A or rab11B-dependent, pathway; 2) ANG II stimulates a PKC-dependent reduction in surface and total BKα, whereas nitric oxide (NO) does not alter BKα surface expression; 3) ANG II did not alter surface or total β1 protein; 4) ANG II-induced reduction in surface BKα is blocked by inhibitors of endocytosis and lysosomal and proteasomal degradation; and 5) ANG II-induced BKα internalization and degradation reduces BK currents in arterial myocytes, elevates myogenic tone, and decreases vasoactive responses to iberiotoxin and NS1619. These data indicate that ANG ...
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A service-level agreement is not the same as a service-level objective. Find out the difference between SLO vs. SLA, the attributes of each and why each is critical to managing service providers.
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder wherein symptoms resembling aspects of aging are manifested at a very early age. It is a genetic condition that occurs due to a de novo mutation in the LMNA gene encoding for the nuclear structural protein lamin A. The lamin family of proteins are thought to be involved in nuclear stability, chromatin structure and gene expression and this leads to heavy effects on the regulation and functionality of the cell machinery. The functional role of the large-conductance calcium-activated potassium channels (BKCa) is still unclear, but has been recently described a strong relationship with their membrane expression, progerin nuclear levels and the ageing process. In this study, we found that: i) the outward potassium membrane current amplitude and the fluorescence intensity of the BKCa channel probe showed higher values in human dermal fibroblast obtained from patients affected by HGPS if
Multiple voltage-gated sodium channels are the primary mediators of cell excitability. They are multimers that consist of the pore-forming alpha subunit and auxiliary beta subunits. Although ion permeability and voltage sensing are primarily determined by the alpha subunit, beta subunits are important modulators of sodium channel function. The purpose of this study was to assess the effect of axotomy on the expression of beta subunits (beta(1), beta(2) and beta(3)) and coexpression of Na(v)1.3 and beta(3) subunits in the dorsal root ganglion (DRG). We used sciatic nerve transection models or spared nerve injury (SNI) models in the rat. In reverse transcriptase-polymerase chain reaction analysis, there were no significant differences between contralateral and ipsilateral DRGs of beta(1) and beta(2) mRNA 3 days after axotomy. beta(3) mRNA expression in ipsilateral DRGs increased significantly compared with contralateral DRGs 3 days after axotomy. In in situ hybridization histochemistry, beta(1) ...
KCNMB3 - KCNMB3 (Myc-DDK-tagged)-Human potassium large conductance calcium-activated channel, subfamily M beta member 3 (KCNMB3), transcript variant 1 available for purchase from OriGene - Your Gene Company.
MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the product of this gene, the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits ...
TY - JOUR. T1 - Angiotensin II stimulates internalization and degradation of arterial myocyte plasma membrane BK channels to induce vasoconstriction. AU - Leo, Marie Dennis. AU - Bulley, Simon. AU - Bannister, John P.. AU - Pushpamangalam Kuruvilla, Korah. AU - Narayanan, Damodaran. AU - Jaggar, Jonathan. PY - 2015/9/15. Y1 - 2015/9/15. N2 - Arterial smooth muscle cells (myocytes) express large-conductance Ca2+- activated K+ (BK) channel α and auxiliary β1 subunits that modulate arterial contractility. In arterial myocytes, β1 subunits are stored within highly mobile rab11A-positive recycling endosomes. In contrast, BKα subunits are primarily plasma membrane-localized. Trafficking pathways for BKα and whether physiological stimuli that regulate arterial contractility alter BKα localization in arterial myocytes are unclear. Here, using biotinylation, immunofluorescence resonance energy transfer (immunoFRET) microscopy, and RNAimediated knockdown, we demonstrate that rab4A-positive early ...
A method of patch clamp recording in hyperbaric oxygen is described which is derived from a method for patch clamping at high hydrostatic pressure. Excised patches equilibrate with hyperbaric oxygen within 10 minutes. Experiments with BK channels expressed in HEK 293 cells showed that 1 MPa O2 caused an increase in the ionic permeability of the patch, an effect accelerated in the presence of ferrous ions. Seal resistance was unaffected. Small negative currents, (VH - 40 to - 65 mV, symmetrical KCl solutions), apparent in skewed all-points amplitude histograms, reduced the signal to noise ratio. In some patches the BK channel activity was inhibited and in others it persisted with the currents becoming irresolvable in the increased noise ...
The properties of Ca(2+)- and voltage-dependent K+ currents and their role in defining membrane potential were studied in cultured rat chromaffin cells. Two variants of large-conductance, Ca2+ and voltage-dependent BK channels, one noninactivating and one inactivating, were largely segregated among patches. Whole-cell noninactivating and inactivating currents resulting from each of these channels were segregated among different chromaffin cells. Cell-to-cell variation in the rate and extent of whole-cell current decay was not explained by differences in cytosolic [Ca2+] regulation among cells; rather, variation was due to differences in the intrinsic properties of the underlying BK channels. About 75% of rat chromaffin cells and patches express inactivating BK current (termed BKi) while the remainder express noninactivating BK current (termed BKs). The activation time course of both currents is similar, as is the dependence of activation on [Ca2+] and membrane potential. However, deactivation of ...
The role of K+ channels in nitric oxide (NO)-induced vasorelaxation has been largely investigated in resistance vessels where iberiotoxin-sensitive MaxiK channels play a predominant role. However, the nature of the K+ channel(s) involved in the relaxation triggered by NO-releasing compounds [nitroglycerin, NTG; NOR 3 [(±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide]] or atrial natriuretic peptide (ANP) in the conduit vessel aorta has remained elusive. We now demonstrate that, in rat aorta, the relaxation due to these vasorelaxants is not affected by the MaxiK channel blocker iberiotoxin (10-7-10-6 M) as was the control vascular bed used (mesenteric artery). The inability of iberiotoxin to prevent NO/ANP-induced aortic relaxations was not due to lower expression of MaxiK in aorta or due to the predominance of iberiotoxin-resistant channels in this conduit vessel. Aortic relaxations were strongly diminished by 4-aminopyridine (4-AP) (≥5 × 10-3 M) or by tetraethylammonium (,2 × 10-3 ...
In the present work, we improve this model neuron by including morphological details. We take the morphological information from identified larval aCC abdominal dorsomedial motoneurons, which innervate the dorsal muscles [4]. A two-compartment version of the model is used to assess effects of changing sodium channel properties. This neuron model allows investigating the effect of sodium channel splice variants by varying half-activation and inactivation voltages and ratio of a persistent component to mimic changes observed in sodium channel current properties in seizure mutants. We further analyze the effect that changes in synaptic input observed in seizure mutants have on the output neuronal activity. ...
A number of interesting and related observations were made. First the authors show that STOC activity at depolarized potentials was enhanced in terms of amplitude, duration, and charge transfer in isolated mesenteric arterial SMCs (ASMCs) from HS rats. Frequency of Ca2+ sparks remained unchanged whereas mean amplitude was increased. In examining the relationship between current and Ca2+ spark amplitude (Figure 2C), the authors convincingly showed that Ca2+ spark-STOC coupling efficiency increased as did the Ca2+ sensitivity of BKCa at micromolar Ca2+ levels in isolated patches. This latter result is expected, given that high Ca2+ promotes a functional interaction between α- and β1-subunits.16,17 Coupled to Western blotting and immunostaining experiments showing β1 but not the α-subunit protein was elevated in HS, are all observations entirely consistent with their hypothesis. Another prediction is that the activation/deactivation kinetics of BKCa would be slowed if β1-subunit levels had a ...
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... binds to the outer face of the large-conductance calcium-activated potassium channels (maxiK or BK channels) with ... Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels. Iberiotoxin is a ... peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus". The ... a potent blocker of the large conductance Ca(2+)-activated K+ channel". Biophysical Journal. 63 (2): 583-90. Bibcode:1992BpJ ...
... s D, E and G have also been found to block activity on large-conductance calcium-activated potassium channels. ... strain HKI0459) with blocking activity on large-conductance calcium-activated potassium channels". Tetrahedron. 63 (2): 435-444 ...
"Entrez Gene: KCNMB4 potassium large conductance calcium-activated channel, subfamily M, beta member 4". Orio P, Rojas P, ... MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of ... cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family". ... "Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 ...
"Entrez Gene: KCNMB1 potassium large conductance calcium-activated channel, subfamily M, beta member 1". Tano, J.-Y.; Gollasch, ... MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of ... "The large conductance potassium channel beta-subunit can interact with and modulate the functional properties of a calcium- ... Calcium-activated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNMB1 gene. ...
"Role of large-conductance calcium-activated potassium channels of coronary arteries in heart preservation". J Heart Lung ... Rottlerin is a potent large conductance potassium channel (BKCa++) opener. BKCa++ is found in the inner mitochondrial membrane ... activated K (BK) channel reduces ischemic injury in rat cardiac myocytes by activating mitochondrial K(Ca) channel". J ... Other BKCa++ channel openers are reported to limit the mitochondrial calcium overload due to ischemia. Rottlerin is also ...
... binds to the large-conductance calcium-activated potassium channel (KCNMA1) and regulates its activity. Moreover, mice ... and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in ... Higgins JJ, Hao J, Kosofsky BE, Rajadhyaksha AM (July 2008). "Dysregulation of large-conductance Ca2+-activated K+ channel ... possibly as a result of dysregulation of calcium-activated potassium channels in the brain (see below) during development. ...
"Entrez Gene: KCNMB2 potassium large conductance calcium-activated channel, subfamily M, beta member 2". Bentrop D, Beyermann M ... Big Potassium (BK) channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to ... 2000). "Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, ... "Cloning and functional expression of two families of beta-subunits of the large conductance calcium-activated K+ channel". J. ...
The second type of potassium channel that tertiapin blocks is the calcium activated large conductance potassium channel (BK). ... inward rectifier potassium channels (Kir) and calcium activated large conductance potassium channels (BK). Tertiapin is a ... KAch channels activate during hyperpolarization, prolonging the cardiac action potential by inflow of potassium ions and ... 8 nM for GIRK1/4 channels and Kd = 2 nM for ROMK1 channels. In contrast to the voltage-gated K+ channels, Kir channels are more ...
CO activates the large conductance calcium-activated potassium channel, BK. Falls in CO that occur as a consequence of hypoxia ... Another mechanism is through oxygen sensitive potassium channels. A drop in dissolved oxygen lead to closing of these channels ... This reduction in the membrane potential opens voltage-gated calcium channels, which causes a rise in intracellular calcium ... "Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel". Science. 306 (5704): 2093-7. doi:10.1126/science ...
In addition, β2 agonists open large conductance calcium-activated potassium channels and thereby tend to hyperpolarize airway ... The combination of decreased intracellular calcium, increased membrane potassium conductance, and decreased myosin light chain ... cAMP decreases calcium concentrations within cells and activates protein kinase A. Both of these changes inactivate myosin ... Asthma aggravation has been observed in patients using large doses of β2 agonists, but if it results from spontaneous course of ...
"Mechanism of iberiotoxin block of the large-conductance calcium-activated potassium channel from bovine aortic smooth muscle". ... the Pi4 binds to SK channels, small conductance Ca2+-activated potassium channels. Pi4 competes with apamin, another SK-channel ... and SK potassium channels. Pi4 binds to Shaker B potassium channels, the Drosophila homologue of the voltage-gated potassium ... Pi4 (α-KTx 6.4) is a short toxin from the scorpion Pandinus imperator that blocks specific potassium channels. The name Pi4 is ...
"The large conductance potassium channel beta-subunit can interact with and modulate the functional properties of a calcium- ... Toda M, Tulic MK, Levitt RC, Hamid Q (2002). "A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 ... 2003). "A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction". Novartis Found ... "Entrez Gene: CLCA1 chloride channel, calcium activated, family member 1". Pawłowski K, Lepistö M, Meinander N, et al. (2006). " ...
... alpha 1 Potassium large conductance calcium-activated channel, subfamily M, alpha 1 Proteasome (prosome, macropain) subunit, ... member A1 Replication protein A1 S100 calcium binding protein A1 Sec61 alpha 1 Serum amyloid A1 Solute carrier family 35 (CMP- ... beta A1 Cyclic nucleotide-gated channel alpha 1 Cyclin A1 Cytochrome P450, family 1, member A1 Defensin, alpha 1 Dystrophin- ... alpha 1 Protein kinase, AMP-activated, alpha 1 Protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting ...
... cause smooth muscle hyperpolarization by opening vascular smooth muscle large-conductance calcium-activated potassium channels ... develop hypertension when fed high sodium or high potassium diets. These and large number of other studies included in the ... large number of epoxygenase substrates other than arachidonic acid, and the large number of activities, some of which may be ... Determination of the role of the EETS in human diseases is made particularly difficult because of the large number of EET- ...
The large-conductance voltage and calcium-activated potassium (MaxiK, BK) channels are intrinsic membrane proteins that ... Unreversibly and weakly blocks the high conductance calcium-activated potassium channels composed of α- and β4-subunits. It ... Slotoxin reversibly blocks the high conductance calcium-activated potassium channels composed of only α-subunits (Kd = 1.5 nM ... Unreversibly blocks the high conductance calcium-activated potassium channels composed of α- and β1-subunits. ...
BK channels (big potassium), are large conductance calcium-activated potassium channels, also known as Maxi-K, slo1, or Kca1.1 ... Calcium-activated potassium channel subunit alpha-1 Calcium-activated potassium channel Voltage-gated potassium channel Zang K ... "The Large Conductance Calcium- and Voltage-activated Potassium Channel (BK) and Epilepsy". CNS & Neurological Disorders Drug ... While calcium activates the channel largely independent of the voltage sensor, magnesium activates the channel by channel by an ...
... and large conductance calcium-activated potassium channel (BKCa) are the two primary channels for potassium secretion. WNK1 ... GABA activates the GABAA receptor which is a Cl− ion channel. Cl− ions will enter the neuron causing hyperpolarization and ... WNK1 regulates potassium channels found in the cortical collecting duct (CCD) and connecting tubule (CNT). Renal outer medullar ... Hence, WNK1 activates CCCs indirectly as an upstream regulator of SPAK/OSR1. In the distal convoluted tubule (DCT), WNK1 is a ...
Small conductance calcium activate potassium channels are quite different from their relatives with larger conductance. The ... Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically ... Brenner, R (2000). "Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta ... Calcium-Activated+Potassium+Channels at the US National Library of Medicine Medical Subject Headings (MeSH) "Calcium-Activated ...
... also known as large conductance calcium-activated potassium channel, ... BK channel Calcium-activated potassium channel Voltage-gated potassium channel GRCh38: Ensembl release 89: ENSG00000156113 - ... "Entrez Gene: KCNMA1 potassium large conductance calcium-activated channel, subfamily M, alpha member 1". Miller C (2000). "An ... "Cloning and expression of a human large-conductance calcium-activated potassium channel". Brain Research. Molecular Brain ...
"The beta subunit increases the Ca2+ sensitivity of large conductance Ca2+-activated potassium channels by retaining the gating ... the calcium-activated potassium channel beta subunit is a family of proteins comprising the beta subunits of calcium-activated ... "Functional role of the beta subunit of high conductance calcium-activated potassium channels". Neuron. 14 (3): 645-50. doi: ... potassium channels. The functional diversity of potassium channels can arise through homo- or hetero-associations of alpha ...
A less closely related member of the SK channels is the intermediate conductance calcium activated potassium channel SK4, also ... The Indian red scorpion (Mesobuthus tamulus) causes a large number of deaths annually especially among young children. Its ... This specific channel block evokes a reduction in the small conductance calcium-dependent potassium channels current. Previous ... which is a highly specific blocker of the high conductance calcium activated potassium channel, and tamulustoxin. Pedarzani P, ...
Other potassium channels like large conductance calcium-dependent potassium channels and sodium chloride dependent potassium ... and is responsible for the activation of calcium-dependent potassium channels. Calcium-activated nonselective cation currents ... voltage gated calcium channels become activated and calcium is able to flow into the cell which usually leads to the release of ... P/Q-type calcium channels are mainly responsible for the release of neurotransmitters that excite, or activate, postsynaptic ...
Large conductance calcium activated potassium channels (BK channels) have recently been demonstrated in the ampulla by cloning ... a small surface area with a high concentration of voltage dependent calcium channels and calcium activated potassium channels. ... One of the first descriptions of calcium activated potassium channels was based on studies of the ampulla of Lorenzini in the ... Clusin, WT; Bennett, MV (February 1977). "Calcium-activated conductance in skate electroreceptors: current clamp experiments". ...
IPA acts on the large-conductance calcium activated K+ channels (BK channels). BK channels are formed by α subunits and ... Kaczorowski, GJ; Knaus, HG; Leonard, RJ; McManus, OB; Garcia, ML (1996). "High-conductance calcium-activated potassium channels ... Isopimaric acid (IPA) is a toxin which acts as a large conductance Ca2+-activated K+ channel (BK channel) opener. IPA ... "Molecular basis of pimarane compounds as novel activators of large-conductance Ca(2+)-activated K(+) channel alpha-subunit". ...
... large-conductance calcium-activated potassium channels MeSH D12.776.157.530.400.600.150.500.500 - large-conductance calcium- ... large-conductance calcium-activated potassium channel beta subunits MeSH D12.776.157.530.400.600.150.750 - small-conductance ... calcium-activated MeSH D12.776.157.530.400.600.150.249 - intermediate-conductance calcium-activated potassium channels MeSH ... calcium-activated potassium channels MeSH D12.776.157.530.400.600.450 - potassium channels, inwardly rectifying MeSH D12.776. ...
... such as small-conductance Ca2+-activated potassium (SK) channels. Calmodulin mediates many crucial processes such as ... "Regulation of calcium channels in smooth muscle: new insights into the role of myosin light chain kinase". Channels. 8 (5): 402 ... It does this by binding various targets in the cell including a large number of enzymes, ion channels, aquaporins and other ... thus affecting the overall levels of calcium in the cell. Calcium pumps take calcium out of the cytoplasm or store it in the ...
... large-conductance calcium-activated potassium channels MeSH D12.776.543.550.425.750.150.500.500 - large-conductance calcium- ... large-conductance calcium-activated potassium channels MeSH D12.776.543.585.400.750.150.500.249 - large-conductance calcium- ... large-conductance calcium-activated potassium channel beta subunits MeSH D12.776.543.550.425.750.150.750 - small-conductance ... large-conductance calcium-activated potassium channel beta subunits MeSH D12.776.543.585.400.750.150.750 - small-conductance ...
This channel, the apamin sensitive, small conductance SK2 potassium channel, is activated by calcium that is likely released ... that is immediately followed by a large outward current, the potassium current, that hyperpolarizes the outer hair cell. When ... system is via a nicotinic class neurotransmitter receptor complex that is coupled with a calcium-activated potassium channel. ... been ruled out that some incoming calcium through the nicotinic alpha9alpha10 channel may also directly activate the SK channel ...
"SK channel" stands for a small conductance calcium activated potassium channel, and the channels are found in the heart. SK ... Early repolarization occurs mainly in males and is associated with a larger potassium current caused by the hormone ... July 2014). "Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human ... The Kv2 channel is characteristically activated slower. The Kv4 channels are characteristically activated rapidly. When Kv2 and ...
SK channels (small conductance calcium-activated potassium channels) are a subfamily of Ca2+-activated K+ channels. They are so ... When a large amount of dopamine accumulates in the cytosol, cell damage is induced due to the build-up of free radicals and ... In addition to being activated by calcium flow through voltage-gated calcium channels, SK channels can be activated by calcium ... "Research interests: Small-conductance calcium-activated potassium channels (SK channels)". Oregon Health & Science University. ...
The NMDA receptor is a glutamate and ion channel protein receptor that is activated when glycine and glutamate bind to it.[2] ... and calcium (Ca2+) ions into the cell and potassium (K+) out of the cell.[5][6][7][8] Ca2+ flux through NMDA receptors in ... The membrane domain contributes residues to the channel pore and is responsible for the receptor's high-unitary conductance, ... When certain NMDA receptor antagonists are given to rodents in large doses, they can cause a form of brain damage called ...
Mg2+ ions close certain types of calcium channels, which conduct positively charged calcium ions into neurons. With an excess ... March 2008). "Magnesium, calcium, potassium, and sodium intakes and risk of stroke in male smokers". Arch. Intern. Med. 168 (5 ... Under ideal conditions the conductance of individual channels can be quantified. This methodology gives the most direct ... Mn2+ can also replace Mg2+ as the activating ion for a number of Mg2+-dependent enzymes, although some enzyme activity is ...
Potassium channels are then activated, and there is an outward current of potassium ions, returning the electrochemical ... Recent Evolution of a Symbiotic Ion Channel in the Legume Family Altered Ion Conductance and Improved Functionality in Calcium ... The large membrane-embedded proteins, in contrast, provide channels through which ions can pass across the membrane. Action ... b) Potassium (K+) ion. c) Sodium channel. d) Potassium channel. e) Sodium-potassium pump.. In the stages of an action potential ...
Calcium 33.6 1.55 52 35% 2.002 0.35 Potassium 72.0 0.89 64 43% 4.291 0.43 ... conductance Mass, relative to Cu, giving same conductance Approx. price (USD per kg) (12/9/2018) Approx. price relative to Cu ... For example, rubber is a material with large ρ and small σ-because even a very large electric field in rubber makes almost no ... Small holes in cell membranes, called ion channels, are selective to specific ions and determine the membrane resistance. ...
... and inward rectifying potassium channels, increasing AMPA and NMDA currents while decreasing potassium conductance.[16] ... Gsα subsequently activates adenylyl cyclase, increasing the intracellular concentration of the second messenger cyclic ... Psychostimulants, such as amphetamine and cocaine, indirectly increase dopamine signaling; large doses and prolonged use can ... increasing intracellular calcium among other cAMP mediated processes. The D2 class of receptors produce the opposite effect, as ...
Hodgkin-Huxley and FitzHugh-Nagumo into a voltage-gated calcium channel model with a delayed-rectifier potassium channel, ... We define the conductance ratio of the ith cylinder as Bi = Gi / G∞, where G. ∞. =. π. d. 3. /. 2. 2. R. i. R. m. {\ ... while GABAB receptors mediate by secondary G-protein-activated potassium channels. This range of mediation produces the ... which converges for large input currents to the previous leak-free model with refractory period.[7] ...
The large purple structure with an arrow represents a transmembrane potassium channel and the direction of net potassium ... Rate of ionic flow through the channel, i.e. single-channel current amplitude, is determined by the maximum channel conductance ... The change in membrane potential can be either large or small, depending on how many ion channels are activated and what type ... For example, sodium or calcium ions rarely pass through a potassium channel. ...
As the extracellular potassium levels increase, potassium conductance is increased so that more potassium leaves the myocyte in ... Above a certain level of potassium the depolarization inactivates sodium channels, opens potassium channels, thus the cells ... Calcium (calcium chloride or calcium gluconate) increases threshold potential through a mechanism that is still unclear, thus ... An ECG of a person with a potassium of 5.7 showing large T waves and small P waves ...
K+: Potassium channel. Calcium-activated. *BK channel *α1. *β1. *β2. *β3. *β4 ... although different hemichannel subunits can impart different single channel conductances, from about 30 pS to 500 pS. ... Large biomolecules, for example, nucleic acid and protein, are precluded from cytoplasmic transfer between cells through gap ... Channel composition influences the function of gap junction channels. Before innexins and connexins were well characterized, ...
... receptors through calcium ion channels. The calcium comes from stores and activate potassium conductance, which causes a pure ... Low-voltage activated calcium ion conductance enhances even larger EPSPs. The hyperpolarization activated nonselective cation ... use potassium channels instead of chloride. They can also block calcium ion channels to hyperpolarize postsynaptic cells. ... These depolarizations activate voltage-dependent calcium channels. They later become hyperpolarizing as the mammal matures. To ...
Two-pore potassium channels (K2Ps) activation[edit]. *Two-pore potassium channels (K2Ps) modulate the potassium conductance ... When large quantities of an anesthetic drug have already been dissolved in the body's fat stores, this can slow its ... This drop in blood pressure may activate a reflexive increase in heartrate, due to a baroreceptor-mediated feedback mechanism. ... Calcium channel blockers. *renin-angiotensin system *ACE inhibitors. *Angiotensin II receptor antagonists ...
... in intracellular calcium concentration by causing an increase in ion conductance through voltage gated calcium channels. This ... Other ion channels can also be disrupted, such as the potassium channels causing inefficient repolarization at the presynaptic ... In diseases such as myasthenia gravis, the end plate potential (EPP) fails to effectively activate the muscle fiber due to an ... Congenital myasthenia gravis is a large group of diseases, since the genetic defects can affect any point in the chain of ...
Potassium channels are the largest and most diverse class of voltage-gated channels, with over 100 encoding human genes. These ... Cherny, V.V.; Markin, V.S.; DeCoursey, T.E. (1995), "The voltage-activated hydrogen ion conductance in rat alveolar epithelial ... Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and ... some channels, such as inward-rectifier potassium ion channels, are activated instead by hyperpolarization. The gate is thought ...
... active calcium-dependent phosphatases dominate over calcium-dependent kinases. As more phosphatases are activated, they tag ... This includes spike generation, a product of nonsynaptic regulation of potassium and other presynaptic ion channels, which ... "Gating of action potential propagation by an axonal A-like potassium conductance in the hippocampus: a new type of non-synaptic ... The storage capacity of synaptic-based memory storage systems is very large, making it an attractive mechanism to study. There ...
... s, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores ... low potassium concentrations in the blood (hypokalemia) and high calcium concentrations in the blood (hypercalcemia). ... When plant aquaporins are silenced, the hydraulic conductance and photosynthesis of the leaf decrease. When gating of plant ... activates the cAMP signaling pathway. This results in aquaporin-2 containing vesicles to increase water uptake and return to ...
Potassium channels Voltage-gated potassium channels e.g., Kvs, Kirs etc. Calcium-activated potassium channels e.g., BKCa or ... Channels belonging to the largest class, which includes the voltage-gated channels that underlie the nerve impulse, consists of ... A variety of ion channel blockers (inorganic and organic molecules) can modulate ion channel activity and conductance. Some ... Calcium-activated potassium channels: This family of channels is activated by intracellular Ca2+ and contains 8 members. Tandem ...
Since the potassium channels within the cell membrane are delayed, any further entrance of sodium activates more and more ... Prolongation of this interval is a result of a delay in sodium and calcium channel inactivation; without proper channel ... then sodium conductance does not increase a sufficient amount to override the resting potassium conductance. In that case, ... For example, a neuron with a large diameter has more ionic channels in its membrane than a smaller cell, resulting in a lower ...
ATP can induce potassium current on Hensen's cells and also elevate the concentration of cytoplasmic calcium in both the inner ... Under negative potential condition, ATP is able to activate a biphasic current which increased the concentration of calcium in ... After the noise exposure, the ATP levels elevated and change the K+ conductance through the P2X receptors by reducing the endo ... Involved receptor and channel mechanisms". Hearing Research. 73 (1): 27-34. doi:10.1016/0378-5955(94)90279-8. PMID 8157503. ...
T-type calcium channels are low voltage activated calcium channels that become deinactivated during cell membrane ... potassium ion) channels, Na+(sodium ion) channels, and other Ca2+(calcium ion) channels. The α1 subunit is composed of four ... Because of this very negative value at which these channels are active, there is a large driving force for calcium going into ... had small single channel conductance, and also were unresponsive to calcium antagonist drugs that were present. These distinct ...
TsTx-IV blocks Ca2+ activated K+ channels of high conductance. Two types of toxin are interesting: α-Scorpion toxins bind at ... By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea. ... Casali, T.A.A.; Gomez, R.S.; Moraes-santos, T.; Gomez, M.V. (1995). "Differential effects of calcium channel antagonists on ... The largest dose produced apnea and death about 70 min later. The lung edema induced by TsTX is blocked by phenobarbital. ...
These channels are thought to be involved in the regulation of different cellular... ... In this chapter we discuss the data obtained for a calcium-activated potassium channel of large unitary conductance. ... In this chapter we discuss the data obtained for a calcium-activated potassium channel of large unitary conductance. These ... Characterization of Large-Unitary-Conductance Calcium-Activated Potassium Channels in Planar Lipid Bilayers. ...
One important target of PKGI in smooth muscle is the large-conductance, calcium-activated potassium (BK) channel, which upon ... Erectile dysfunction in mice lacking the large-conductance calcium-activated potassium (BK) channel J Physiol. 2005 Sep 1;567( ... One important target of PKGI in smooth muscle is the large-conductance, calcium-activated potassium (BK) channel, which upon ... Potassium Channels, Calcium-Activated / deficiency * Potassium Channels, Calcium-Activated / genetics * Potassium Channels, ...
Large conductance, calcium-activated potassium (BK) channels play a prominent role in vertebrate hair cell function. BK ... β Subunits Modulate Alternatively Spliced, Large Conductance, Calcium-Activated Potassium Channels of Avian Hair Cells. ... β Subunits Modulate Alternatively Spliced, Large Conductance, Calcium-Activated Potassium Channels of Avian Hair Cells ... β Subunits Modulate Alternatively Spliced, Large Conductance, Calcium-Activated Potassium Channels of Avian Hair Cells ...
KCNMB4, potassium calcium-activated channel subfamily M regulatory beta subunit 4. Orthology source: HomoloGene, HGNC ... J:250373 Whitmire LE, et al., Downregulation of KCNMB4 expression and changes in BK channel subtype in hippocampal granule ... potassium large conductance calcium-activated channel, subfamily M, beta member 4. * Synonyms ...
A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by ... either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical ... Potassium Channels: 2108*Calcium-Activated Potassium Channels: 183*Large-Conductance Calcium-Activated Potassium Channels: 162* ... Potassium Channels: 2108*Calcium-Activated Potassium Channels: 183*Large-Conductance Calcium-Activated Potassium Channels: 162* ...
large-conductance calcium-activated potassium channel. EDP. epoxydocosapentaenoic acid. EEQ. epoxyeicosaquatraenoic acid. DHDP ... of Docosahexaenoate Potently Dilate Coronary Arterioles by Activating Large-Conductance Calcium-Activated Potassium Channels. ... of Docosahexaenoate Potently Dilate Coronary Arterioles by Activating Large-Conductance Calcium-Activated Potassium Channels. ... of Docosahexaenoate Potently Dilate Coronary Arterioles by Activating Large-Conductance Calcium-Activated Potassium Channels. ...
anti-Potassium Large Conductance Calcium-Activated Channel, Subfamily M, beta Member 1 (KCNMB1) antibody (Alexa Fluor 647) ... Itemanti-Potassium Large Conductance Calcium-Activated Channel, Subfamily M, beta Member 1 (KCNMB1) antibody (Alexa Fluor 647) ... anti-Potassium Large Conductance Calcium-Activated Channel, Subfamily M, beta Member 1 (KCNMB1) antibody (Alexa Fluor 647) from ... anti-Potassium Large Conductance Calcium-Activated Channel, Subfamily M, beta Member 1 (KCNMB1) antibody (Alexa Fluor 647) ...
the single-channel slope conductance was linear in the voltage range -60/+60 mV, and was 207±19 pS. Na+ ions were not ... Channel activity increased with the cytoplasmic free Ca2+ concentration ([Ca2+]i) with a Hill plot giving a half-saturating [ ... The resting activity was consistent with a [Ca2+]i ,100 nM and the increased channel activity evoked by ionomycin was ... Ionomycin (1-10 μM) increased BK channel activity in the cell-attached recording configuration. ...
Keywords:Potassium channel, BK channel, epilepsy, large conductance, calcium, voltage-activated.. Abstract:Background & ... The large conductance, calcium- and voltage-activated potassium channels (BK) are widely distributed channel proteins which ... The large conductance, calcium- and voltage-activated potassium channels (BK) are widely distributed channel proteins which ... The Large Conductance Calcium- and Voltage-activated Potassium Channel (BK) and Epilepsy. Author(s): Kai Zang, Department of ...
Myc-DDK-tagged ORF clone of Homo sapiens potassium large conductance calcium-activated channel, subfamily M beta member 3 ( ... home , products , origene , myc-ddk-tagged orf clone of homo sapiens potassium large conductance calcium-activated channel, ... Myc-DDK-tagged ORF clone of Homo sapiens potassium large conductance calcium-activated channel, subfamily M beta member 3 ( ... Myc-DDK-tagged ORF clone of Homo sapiens potassium large conductance calcium-activated channel, subfamily M beta member 3 ( ...
Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 4, Rea, item number: VMPS-3286 from ... Kcnmb4, Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 4, Rea ... Customer review for "Kcnmb4, Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 4, Rea" ... Product information "Kcnmb4, Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 4, Rea" ...
Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 4 (Kcnmb4), (10ug), 10 µg. ... Home » cDNA » Mouse cDNA » Kcnmb4 (untagged) - Mouse potassium large conductance calcium-activated channel, subfamily M, beta ... MC210183 Kcnmb4 (untagged) - Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 4 (Kcnmb4 ... Properties for Kcnmb4 (untagged) - Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 4 ( ...
Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 1 (Kcnmb1), (10ug), 10 µg. ... Home » cDNA » Mouse cDNA » Kcnmb1 (untagged) - Mouse potassium large conductance calcium-activated channel, subfamily M, beta ... MC207312 Kcnmb1 (untagged) - Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 1 (Kcnmb1 ... Properties for Kcnmb1 (untagged) - Mouse potassium large conductance calcium-activated channel, subfamily M, beta member 1 ( ...
... of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels. ... of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels, ... of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels. ... of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels. ...
potassium large conductance calcium-activated channel, subfamily M, beta member 1 MGI ID ...
The large-conductance calcium-activated potassium channels (BKCa) and voltage-gated sodium channels were expressed in cortical ... roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels. ... Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons. Am J ... The large conductance Ca2+-activated K+ (BKCa) channel currents in response to resveratrol were examined in the condition of ...
... 0-9. A. B. C. D. E. F. G. H. I. ... The large conductance Ca2+- and voltage-activated potassium (BK) channel is activated via two important cellular signaling ... Large-conductance Ca2+-activated K+ (BK) channels have a major role in driving the diurnal patterns of spontaneous firing in ... Though the BK channel is encoded via a single gene, Kcnma1, currents produced by this channel exhibit a large degree of ...
title = "Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is ... T1 - Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is ... Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is decreased ... Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is decreased ...
The family of SLO channels apparently evolved from voltage-dependent potassium channels, but acquired a large conserved ... channels encoded by the Slo gene family are among the largest and most complex of the extended family of potassium channels. ... Large-Conductance Calcium-Activated Potassium Channels / genetics * Large-Conductance Calcium-Activated Potassium Channels / ... Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / genetics * Large-Conductance Calcium-Activated Potassium ...
2002) Multiple regulatory sites in large-conductance calcium-activated potassium channels. Nature 418(6900):880-884. ... 2009) Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat ... 2002) Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels ... Because large-conductance Ca2+- and voltage-activated K+ (Slo1 BK) channels are important in regulation of vascular tone (13, ...
Large-Conductance Calcium- and Voltage-Activated Potassium Channels (BK). BK channels are large-conductance calcium- and ... Alcohol tolerance in large-conductance, calcium-activated potassium channels of CNS terminals is intrinsic and includes two ... Somatic localization of a specific large-conductance calcium-activated potassium channel subtype controls compartmentalized ... Channels underlying neuronal calcium-activated potassium currents. Prog. Neurobiol 2002, 66, 345-353. [Google Scholar] ...
Characterisation of large-conductance calcium-activated potassium channels (BKCa) in human NT2-N cells. Brain Research 1129 (1 ... Characterisation of large-conductance calcium-activated potassium channels (BKCa) in human NT2-N cells ...
Functional coupling of beta(3)-adrenoceptors and large conductance calcium-activated potassium channels in human uterine ... adrenoceptors and large conductance calcium-activated potassium channels in human uterine myocytes. Journal Of Clinical ... Single-channel recordings identified the BKCa channel as a target of BRL37344. BRL37344 significantly increased the open state ... Maxi-K+ channels (BKCa) play a significant role in modulating cell membrane potential and excitability.Objective: This study ...
Inactivation of large-conductance, calcium-activated potassium channels in rat cortical neurons. / Smith, M. A; Ashford, M.L.J. ... Inactivation of large-conductance, calcium-activated potassium channels in rat cortical neurons. In: Neuroscience. 1999 ; Vol. ... Inactivation of large-conductance, calcium-activated potassium channels in rat cortical neurons. Neuroscience. 1999 Nov;95(1): ... Smith, M. A., & Ashford, M. L. J. (1999). Inactivation of large-conductance, calcium-activated potassium channels in rat ...
... and ionic channels remain unclear. We examined the hypothesis that hippocampal NO deficit impairs the activity of large ... conductance calcium-activated potassium (BK) channels in rats with chronic IH, mimicking conditions in patients with sleep ... We found that the open probability of BK channels remarkably decreased in the CA1 pyramidal neurons in a time-dependent manner ... NO donors, SNP or DETA/NO, significantly restored the activity of BK channels in the IH neurons, which was prevented by ...
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits. *Large-Conductance Calcium-Activated Potassium Channel ... Large-Conductance Calcium-Activated Potassium Channel alpha Subunits. *Large-Conductance Calcium-Activated Potassium Channel ... Large-conductance calcium-activated potassium (BK(Ca)) channels are composed of the pore-forming alpha-subunit and the ... Functional effects of auxiliary beta4-subunit on rat large-conductance Ca(2+)-activated K(+) channel.. Ha TS1, Heo MS, Park CS. ...
... postconditioning against myocardial infarction is mediated by large-conductance calcium-activated potassium channels: BAPCAP2-2 ...
Oxidative regulation of large conductance calcium-activated potassium channels.. Tang XD, Daggett H, Hanner M, Garcia ML, ... Modulation of potassium channel function by methionine oxidation and reduction.. Ciorba MA, Heinemann SH, Weissbach H, Brot N, ... Regulation of voltage-dependent K+ channels by methionine oxidation: effect of nitric oxide and vitamin C. ... Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling. ...
4.1.3. Large Conductance Calcium-Activated (BK) Potassium Channels in SAH. Whether BK channels are impacted by SAH and ... and large-conductance calcium-activated (BK) potassium channels. Kir2.1 mRNA and protein could be identified in basilar ... Although typically classed with the high-voltage-activated Ca2+ channels, R-type calcium channels are activated at potentials ... N. Gokina, R. Bevan, C. Walters, and J. Bevan, "Calcium-activated potassium channels regulate membrane potential and tone and ...
The large-conductance, voltage-gated, calcium (Ca2+)-activated potassium channel (BKCa) plays an important role in regulating ... The large-conductance, voltage-gated, calcium (Ca2+)-activated potassium channel (BKCa) plays an important role in regulating ... 1993) Characterization of large-conductance, calcium-activated potassium channels from human myometrium. Am J Obstet Gynecol ... The predominant K+ channel in the myometrium is the large-conductance, voltage-gated, Ca2+-activated K+ channel (BKCa), also ...
  • We investigated the functional role of BK channels in the corpus cavernosum utilizing a knock-out mouse lacking the Slo gene (Slo-/-) responsible for the pore-forming subunit of the BK channel. (nih.gov)
  • BK channels in hair cells are encoded by the alternatively spliced slo gene and may include an accessory β subunit. (jneurosci.org)
  • Addition of the β subunit increased steady-state calcium affinity, raised the Hill coefficient for calcium binding, and slowed channel deactivation rates, resulting in eight functionally distinct channels. (jneurosci.org)
  • While regulation of expression of the BK channel gene can account for part of the diurnal difference in excitability of SCN neurons, we hypothesized that daily regulation of BK current properties in the SCN via β-subunit association, alternative splicing, and control of Ca2+ sources limits a role for BK currents in setting firing frequency during the day. (umaryland.edu)
  • Expression of the α subunit of the Maxi-K channel was significantly decreased ~40% while the expression of the β1 subunit was increased ~2-fold at the mRNA level. (elsevier.com)
  • Increased expression of the β1 subunit points to a compensatory reaction to decreased Maxi-K channel activity. (elsevier.com)
  • We report here that DHA with an EC 50 of ∼500 nM rapidly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit β1, increasing currents by up to ∼20-fold. (pnas.org)
  • Functional effects of auxiliary beta4-subunit on rat large-conductance Ca(2+)-activated K(+) channel. (nih.gov)
  • Large-conductance calcium-activated potassium (BK(Ca)) channels are composed of the pore-forming alpha-subunit and the auxiliary beta-subunits. (nih.gov)
  • To understand the physiological roles of the beta4-subunit on the BK(Ca) channel alpha-subunit (Slo), we isolated a full-length complementary DNA of rat beta4-subunit (rbeta4), expressed heterolgously in Xenopus oocytes, and investigated the detailed functional effects using electrophysiological means. (nih.gov)
  • Because BK(Ca) channels are known to modulate neuroexcitability and the expression of the beta4-subunit is highly concentrated in certain subregions of brain, the electrophysiological properties of individual neurons should be affected profoundly by the expression of this second subunit. (nih.gov)
  • Representative current traces from excised patches expressing rSlo and rSlo/r β 4 channels and effects of r β 4-subunit on the conductance-voltage relationship of rSlo channels. (nih.gov)
  • Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2 , which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. (nature.com)
  • Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. (nature.com)
  • Calcium-activated potassium channel subunit alpha-1 also known as large conductance calcium-activated potassium channel, subfamily M, alpha member 1 (KCa1.1), or BK channel alpha subunit, is a voltage gated potassium channel encoded by the KCNMA1 gene and characterized by their large conductance of potassium ions (K+) through cell membranes. (wikipedia.org)
  • Each monomer of the channel-forming alpha subunit is the product of the KCNMA1 gene. (wikipedia.org)
  • Each BK channel alpha subunit consists of (from N- to C-terminal): A unique transmembrane domain (S0) that precedes the 6 transmembrane domains (S1-S6) conserved in all voltage-dependent K+ channels. (wikipedia.org)
  • Like Slo1 subunits responsible for the Ca(2+) and voltage-activated BK-type channel, the Slo3 alpha subunit contains a pore module with homology to voltage-gated K(+) channels and also an extensive cytosolic C terminus thought to be responsible for ligand dependence. (semanticscholar.org)
  • MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. (genecards.org)
  • The protein encoded by this gene is an auxiliary beta subunit which slows activation kinetics, leads to steeper calcium sensitivity, and shifts the voltage range of current activation to more negative potentials than does the beta 1 subunit. (genecards.org)
  • KCNMB4 (Potassium Calcium-Activated Channel Subfamily M Regulatory Beta Subunit 4) is a Protein Coding gene. (genecards.org)
  • Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. (genecards.org)
  • Identification of a putative regulatory subunit of a calcium-activatedpotassium channel in the dup(3q) syndrome region and a related sequence on22q11.2.Genomics. (tcdb.org)
  • KCNMB3 has significant sequence similarity to the regulatory subunit of the large-conductance calcium-activated potassium channel. (tcdb.org)
  • Arterial myocytes also express LRRC26, an auxiliary γ subunit that elevates channel voltage sensitivity to induce vasodilation ( 12 ). (physiology.org)
  • The beta-subunit exhibits its effect on the Maxi K+ channel by effectively decreasing by 5- to 10- fold the concentration of calcium required to keep the pore open. (thermofisher.com)
  • The brain-specific auxiliary subunit β4 alters channel Ca ++ - and voltage-sensitivity, and β4 knock-out animals exhibit spontaneous seizures. (pubmedcentralcanada.ca)
  • Using a novel genetic tag to track the cellular location of the pore-forming BKα subunit in living cells, we find that β4 expression profoundly reduces surface localization of BK channels via a C-terminal ER retention sequence. (pubmedcentralcanada.ca)
  • Which Channel Subunit Is Really Fueling the Fire? (ahajournals.org)
  • Consistent with this, a gain-of-function mutation in the human β1-subunit gene (KCNMB1), involving an increase in the apparent Ca 2+ and voltage sensitivity of the channel, protected patients against diastolic hypertension. (ahajournals.org)
  • Another prediction is that the activation/deactivation kinetics of BK Ca would be slowed if β1-subunit levels had a functional impact on the number of channels expressing both subunits at the membrane. (ahajournals.org)
  • The large conductance Ca 2+ -activated K + (BK) channel β1-subunit (BK-β1) is a key modulator of BK channel electrophysiology and the downregulation of BK-β1 protein expression in vascular smooth muscle cells (SMCs) underlies diabetic vascular dysfunction. (diabetesjournals.org)
  • The presence of BK-β1 enhances BK channel α-subunit sensitivity to Ca 2+ , allowing channel activation in the physiological range of Ca 2+ concentrations and membrane potentials ( 5 - 7 ). (diabetesjournals.org)
  • Furthermore, we found that silencing the β3 but not the β1 subunit with siRNA reduced KCa1.1 channel density at the plasma membrane of RA-FLS and inhibited RA-FLS invasiveness. (biomedcentral.com)
  • However, paxilline is a lipophilic small molecule that blocks all KCa1.1 channels found in major organs, regardless of channel subunit composition [ 13 - 15 ], and can cross cell membranes as well as the blood-brain barrier. (biomedcentral.com)
  • Iberiotoxin-sensitive voltage- and [Ca2+]-activated K+ currents, the latter activated by local transient calcium releases (calcium sparks), were present in Slo+/+ CCSM cells, but absent in Slo-/- cells. (nih.gov)
  • Resveratrol concentration-dependently increased the current amplitude and the opening activity of BK Ca channels, but suppressed the amplitude of voltage-gated sodium currents. (biomedcentral.com)
  • Our data demonstrated that resveratrol activated BK Ca channels, but inhibited voltage-gated sodium currents. (biomedcentral.com)
  • BK K+ currents are larger at night, correlating with reduced neuronal excitability. (umaryland.edu)
  • BK currents undergo multi-level regulation by genetic and posttranslational mechanisms as well as functional coupling to Ca2+ channels. (umaryland.edu)
  • Though the BK channel is encoded via a single gene, Kcnma1, currents produced by this channel exhibit a large degree of phenotypic variability across different cell types, indicating regulation of the BK channel can influence BK current properties. (umaryland.edu)
  • Using patch-clamp electrophysiolgy we demonstrate that BK current properties in the SCN are diurnally regulated, with smaller BK currents during the day found to be due to BK channel inactivation, Ca2+ source regulation and alternative splicing, rather than simply a decrease in BK channel expression. (umaryland.edu)
  • Patients orOther Participants: Myometrial biopsies were obtained at elective cesarean delivery.Intervention: No intervention was applied.Main Outcome Measures: Open state probability of single channel recordings, whole cell currents, and myometrial contractile activity were measured.Results: Single-channel recordings identified the BKCa channel as a target of BRL37344. (nuigalway.ie)
  • Small conductance Ca2+-activated K+ channel knock-out mice reveal the identity of calcium-dependent afterhyperpolarization currents. (naver.com)
  • This makes the BK channel an important negative feedback system linking increases in intracellular calcium to outward hyperpolarizing potassium currents. (frontiersin.org)
  • Outward potassium ion currents activated upon depolarization would counteract the depolarizing action of inward currents carried either by sodium ion (Na+) or Ca2+. (novapublishers.com)
  • ANG II-mediated BK channel degradation reduced BK currents in isolated myocytes and functional responses to iberiotoxin, a BK channel blocker, and NS1619, a BK activator, in pressurized (60 mmHg) cerebral arteries. (physiology.org)
  • These data describe a unique mechanism by which ANG II inhibits arterial myocyte BK currents, by reducing surface channel number, to induce vasoconstriction. (physiology.org)
  • Deletion of RBP s in calyx of Held synapses decreased and decelerated presynaptic BK ‐currents and depleted BK ‐channels from active zones. (embopress.org)
  • Expression of RBP 2 shifts the voltage‐dependence of BK α‐channels in HEK 293T cells and deletion of RBP s decreases presynaptic BK ‐currents. (embopress.org)
  • The large-conductance K + channel (BK channel) can control neural excitability, and enhanced channel currents facilitate high firing rates in cortical neurons. (pubmedcentralcanada.ca)
  • In hippocampal CA3 neurons from C57BL/6 mice with endogenously high β4 expression, whole-cell BK channel currents display none of the characteristic properties of BKα+β4 channels observed in heterologous cells. (pubmedcentralcanada.ca)
  • Indeed, genetic knock-out of β4 results in larger BK channel currents gated by action potential (AP) firing and is associated with increased firing activity and spontaneous seizures in mice [1] . (pubmedcentralcanada.ca)
  • Techniques include use of in vivo mammalian preparations as well as in vitro slices and acutely dissociated neurons for recordings of synaptic activities and membrane properties, using patch-clamp techniques to study whole cell currents and membrane channels. (stanford.edu)
  • Intracellular Mg(2+) also modulates BK channels in multiple ways with opposite effects on channel function.We have confirmed this result by studying macroscopic currents of the mslo1 channel.We discovered that Mg(2+) also binds to Ca(2+) sites and competitively inhibits Ca(2+)-dependent activation. (nih.gov)
  • We have confirmed this result by studying macroscopic currents of the mslo1 channel. (nih.gov)
  • MPA(-) increased currents and MTSET(+) decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. (nih.gov)
  • A-C) Representative records of outward currents through single BK channels held at +180 mV before and after applications of thiol reagents to wt and mutated channels. (nih.gov)
  • however, reducing channel activity with intracellular calcium destabilized inactivation. (dundee.ac.uk)
  • The levels of endogenous NO and intracellular calcium in the CA1 region of the hippocampal slices were measured respectively by electrochemical microsensors and spectrofluorometry. (naver.com)
  • Also, the level of protein expression of neuronal NO synthase was markedly lessened in the IH neurons with decreased intracellular calcium response to hypoxia. (naver.com)
  • The large conductance calcium- and voltage-activated K + channel (KCa1.1, BK, MaxiK) is ubiquitously expressed in the body, and holds the ability to integrate changes in intracellular calcium and membrane potential. (frontiersin.org)
  • BK channels are activated (opened) by changes in membrane electrical potential and/or by increases in concentration of intracellular calcium ion (Ca2+). (wikipedia.org)
  • Transient elevations in intracellular calcium are sufficient to induce sustained responsiveness to the neurotrophic factor bFGF. (semanticscholar.org)
  • Intracellular calcium release at fertilization in the sea urchin egg. (semanticscholar.org)
  • Here, we explored the particular association between behavior of the voltage fluctuations in the inter-spike segment (VFIS) and the inter-spike intervals (ISI) of F1 pacemaker neurons from H. aspersa, by disturbing the intracellular calcium handling with cadmium and caffeine. (deepdyve.com)
  • Our findings endorse that the behavior of the VFIS appears associated to the activation of different populations of ionic channels, which establish the neural membrane potential and are mediated by the intracellular calcium handling. (deepdyve.com)
  • Maxi K+ differs from most other potassium channels in that its activation is controlled by both increases in intracellular calcium and by membrane depolarization. (thermofisher.com)
  • The core of the channel, which is similar to other potassium channels, is a Maxi K+ alpha homotetramer that contains both a voltage sensor and an intracellular calcium binding domain. (thermofisher.com)
  • The effect of pH on cerebral vascular tone is mediated by nitric oxide (NO), prostanoids, cyclic nucleotides, potassium channels, and intracellular calcium. (asahq.org)
  • Alternative splicing of the slo -α channel message provides intrinsic variability in gating kinetics that is expanded to a wider range of tuning by modulation with β subunits. (jneurosci.org)
  • Co-expression of chick hair cell slo -α with quail β subunits greatly increased open probability at negative membrane potentials, giving the expressed channels a calcium and voltage sensitivity close to that of native hair cell BK channels. (jneurosci.org)
  • To determine the effect of PUO on the expression of the Maxi-K channel α and β1 subunits and in vitro detrusor contractility. (elsevier.com)
  • A cysteine-rich motif confers hypoxia sensitivity to mammalian large conductance voltage- and Ca-activated K (BK) channel alpha-subunits. (naver.com)
  • Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones. (naver.com)
  • In situ hybridization revealed the presence of different BK channel splice variants (X1 +24 , X2 +92 , SS2 +174 and SS4 +81 ) in combination with β 1, β 2, and β 4 subunits in rat cerebral arteries [ 13 ]. (hindawi.com)
  • Structurally the channel consist of four pore-forming BK α-subunits, each with 7 transmembrane segments and an extracellular N-terminus. (frontiersin.org)
  • Modulatory beta subunits (encoded by KCNMB1, KCNMB2, KCNMB3, or KCNMB4) can associate with the tetrameric channel. (wikipedia.org)
  • Arterial smooth muscle cells (myocytes) express large-conductance Ca 2+ -activated K + (BK) channel α and auxiliary β1 subunits that modulate arterial contractility. (physiology.org)
  • Functional BK channels contain four α subunits that assemble to form a K + -selective pore ( 16 , 39 ). (physiology.org)
  • BK accessory β and γ subunits modify channel properties and can exhibit tissue-specific expression to elicit these effects in a cell type-dependent manner ( 3 , 39 , 43 ). (physiology.org)
  • β1 Subunits elevate channel apparent Ca 2+ sensitivity into a micromolar concentration range sufficient to permit sensing of local intracellular Ca 2+ transients termed Ca 2+ sparks, which control BK channel activity in arterial myocytes ( 18 - 20 ). (physiology.org)
  • Similar to an archeon Ca 2+ -activated K + channel, MthK, each of four α subunits of BK Ca may contain two cytosolic RCK domains and eight of which may form a gating ring. (rupress.org)
  • BK Ca possesses common structural features of homotetrameric voltage-gated K + channels, including an ion-selective pore formed by transmembrane segments S5 and S6 and a selectivity filter from four α-subunits, and a voltage-sensing module formed by transmembrane segments S1-S4. (rupress.org)
  • Functional vascular BK channels are composed of the pore-forming α-subunits and the regulatory β1-subunits (BK-β1) in 4:4 stoichiometry. (diabetesjournals.org)
  • On the other hand, KCa1.1 channels can also contain different accessory subunits with restricted tissue distribution that regulate channel kinetics and pharmacology. (biomedcentral.com)
  • Our findings suggest the KCa1.1 channel composed of α and β3b subunits as an attractive target for the therapy of RA. (biomedcentral.com)
  • As cerebellar Purkinje cells express the major regulatory elements of calcium control and represent the sole integrative output of the cerebellar cortex, changes in neural activity- and calcium-mediated membrane properties of these cells are expected to provide important insights into both intrinsic and network physiology of the cerebellum. (biomedsearch.com)
  • Molecular physiology and pathology of Ca2+-conducting channels in the plasma membrane of mammalian sperm. (semanticscholar.org)
  • The family of SLO channels apparently evolved from voltage-dependent potassium channels, but acquired a large conserved carboxyl extension, which allows channel gating to be altered in response to the direct sensing of several different intracellular ions, and by other second-messenger systems, such as those activated following neurotransmitter binding to G-protein-coupled receptors (GPCRs). (nih.gov)
  • When expressed together with rat Slo (rSlo), rbeta4 profoundly altered the gating characteristics of the Slo channel. (nih.gov)
  • Single BK(Ca) channels composed of rSlo and rbeta4 also exhibited slower kinetics for steady-state gating compared with rSlo channels. (nih.gov)
  • A cytoplasmic C-terminal domain (CTD) consisting of a pair of RCK domains that assemble into an octameric gating ring on the intracellular side of the tetrameric channel. (wikipedia.org)
  • Available X-ray structures include: 3U6N​ - Open structure of the BK channel gating ring 3MT5​ - Crystal structure of the human BK gating apparatus 3NAF​ - Structure of the intracellular gating ring from the human high-conductance Ca2+ gated K+ channel (BK Channel) BK channels are pharmacological targets for the treatment of stroke. (wikipedia.org)
  • Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP. (semanticscholar.org)
  • TGFbeta1 regulates the gating properties of intermediate-conductance KCa channels in developing parasympathetic neurons. (semanticscholar.org)
  • Modulates gating properties by producing a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction, and in the absence of calcium. (genecards.org)
  • Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. (genecards.org)
  • Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. (genecards.org)
  • The second is the electrical capacitance energy W C [ q ] , representing "global" gating charge displacement, and is equal to the product of total gating charge per channel times the first moment ( V M ) of normalized capacitance (slope of Q-V curve). (rupress.org)
  • Plots of W H [ g ] and W C [ q ] versus voltage and Ca 2+ potential can be used to measure thermodynamic parameters in a model-independent fashion of the core gating constituents (pore, voltage-sensor, and Ca 2+ -binding domain) of BK channel. (rupress.org)
  • In many channels, gating is strongly influenced by a ring of accessory domains acting as efficient conveyers of thermal, mechanical, or chemical energy to the pore's central gating apparatus. (rupress.org)
  • An indirect method of studying voltage gating and other means of environmental sensitivity is to measure the conductance G , a specific marker of pore activation. (rupress.org)
  • Calcium sensors (K) are situated beneath the membrane plane, where they form a structure known as the gating ring. (rupress.org)
  • The structure of the MthK channel suggests that the RCK domains reorient with one another upon Ca 2+ binding to change the gating ring conformation and open the activation gate. (rupress.org)
  • However, the nature of conformational changes in the BK Ca gating ring during Ca 2+ -dependent activation may not be identical to that in the MthK channels. (rupress.org)
  • Further improvement of this approach should permit direct observation of the gating motion of a single-channel protein. (physiology.org)
  • On the transcriptional level, extensive alternative splicing gives rise to channels with altered Ca 2+ sensitivity, channel kinetics, localization and hormone sensitivity (for review see Shipston, 2001 ). (frontiersin.org)
  • The BKα COOH terminus contains RCK (regulator of conductance for K + ) domains and a "Ca 2+ bowl," which endow Ca 2+ sensitivity ( 23 ). (physiology.org)
  • Both approaches demonstrated that HBSMC membranes contained large-conductance channels (>200 pS) with both calcium and voltage sensitivity, all of which is characteristic of the BK(Ca) channel. (umassmed.edu)
  • Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. (biomedcentral.com)
  • for example, the sensitivity of many voltage-gated channels to voltage changes easily surpasses the sensitivity of man-made transistors ( 37 ). (physiology.org)
  • However, coexpression of the mslo1 core and mslo3 tail produces channels with Mg(2+) sensitivity similar to mslo1 channels, indicating that Mg(2+) sites differ from Ca(2+) sites. (nih.gov)
  • The properties of single Ca2+-activated K+ (BK) channels in neonatal rat intracardiac neurons were investigated using the patch-clamp recording technique. (edu.au)
  • However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. (biomedcentral.com)
  • The large-conductance calcium-activated potassium channels (BK Ca ) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. (biomedcentral.com)
  • As BK Ca channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol. (biomedcentral.com)
  • Voltage-gated sodium channels in cardiomyocytes [ 47 ] and rat dorsal root ganglion neurons [ 21 ] are also blocked by resveratrol. (biomedcentral.com)
  • Despite this, the effects of resveratrol on the membrane properties and the ion channels of neurons have not yet been fully determined. (biomedcentral.com)
  • Large-conductance Ca2+-activated K+ (BK) channels have a major role in driving the diurnal patterns of spontaneous firing in SCN neurons. (umaryland.edu)
  • Lastly, this investigated a potential mechanism by which LTCCs contribute to firing rate in SCN neurons by examining their ability to activate BK channels under controlled conditions. (umaryland.edu)
  • Furthermore, regulation of current properties, as opposed to changing expression of the channel, may act as a mechanism through which excitability can be modulated in various neurons. (umaryland.edu)
  • Inside-out patch recordings from rat acutely dissociated cerebral cortical neurons revealed time and voltage-dependent activity of a large-conductance calcium-activated potassium channel. (dundee.ac.uk)
  • We found that the open probability of BK channels remarkably decreased in the CA1 pyramidal neurons in a time-dependent manner with the IH treatment, without changes in the unitary conductance and reversal potential. (naver.com)
  • NO donors, SNP or DETA/NO, significantly restored the activity of BK channels in the IH neurons, which was prevented by blockade of S-nitrosylation with NEM or MTSES but not by inhibition of the cGMP pathway with ODQ or 8-bromo-cGMP. (naver.com)
  • Various pharmaceutical companies developed synthetic molecules activating these channels in order to prevent excessive neurotoxic calcium entry in neurons. (wikipedia.org)
  • The developmental expression of Ca2+-activated K+ channels (KCa) in chick ciliary ganglion (CG) neurons is regulated by a target-derived avian isoform of TGFbeta1, which evokes a robust increase in the number of functional large-conductance (BK) KCa channels but which produces no change in their kinetics. (semanticscholar.org)
  • However, CG neurons express multiple KCa channel subtypes. (semanticscholar.org)
  • [7,8] Tetrodotoxin, which blocks sodium channels and prevents neuronal depolarization, does not reduce CO 2 -mediated cerebral vasodilation, indicating that depolarization of perivascular nerves or parenchymal neurons is not important. (asahq.org)
  • Sensitization of sodium channels by cystathionine β-synthetase activation in colon sensory neurons in adult rats with neonatal maternal deprivation. (abnova.com)
  • Somatosensory neurons that sense touch branch out within the skin and rely on a set of mechano-electrical transduction channels distributed within their dendrites to detect mechanical stimuli. (stanford.edu)
  • Background & Objective: The large conductance, calcium- and voltage-activated potassium channels (BK) are widely distributed channel proteins which exist in virtually every cell type of mammals and function to influence membrane excitability and Ca2+ signaling. (eurekaselect.com)
  • Potassium ion channel activity is also essentially regulated by the intracellular signal transduction pathways, such as receptors' (G proteins) second messenger molecules processes in the physiological condition. (novapublishers.com)
  • large-conductance Ca 2+ -activated K + (BKα, MaxiK, Slo1 ) channels are seven-transmembrane proteins with a short extracellular amino (NH 2 ) and long intracellular carboxy (COOH) terminus ( 14 , 16 ). (physiology.org)
  • Here, we show that RBP s (for RIM ‐binding proteins), which are evolutionarily conserved active zone proteins containing SH 3‐ and FN 3‐domains, directly bind to BK ‐channels. (embopress.org)
  • Direct interaction between large‐conductance potassium BK ‐channels and scaffold RIM ‐binding proteins ( RBP s) in the nerve presynaptic terminal is required for recruitment of BK α to active zone Ca 2+ ‐channels and efficient control of neurotransmitter release. (embopress.org)
  • Recently, large scale gene expression profiling identified candidate alcohol responsive genes in human brains [ 6 - 10 ], including genes that encode proteins involved in myelination, neurodegeneration, protein trafficking as well as calcium, cAMP, and thyroid signaling pathways. (biomedcentral.com)
  • Potassium channels are a group of ubiquitously expressed proteins that serve numerous functions in excitable and non-excitable cells. (thermofisher.com)
  • Thus recordings of the change in the fluorescence emission allow direct real-time observation of conformational rearrangements in channel proteins during channel activation. (physiology.org)
  • High-conductance, 'big' potassium (BK) channels encoded by the Slo gene family are among the largest and most complex of the extended family of potassium channels. (nih.gov)
  • Using a combination of biochemistry, electrophysiology, and imaging techniques, we now show that NMDARs have a key role in mediating the effect of leptin to modulate -cell electrical activity by promoting AMP-activated protein kinase (AMPK)-dependent trafficking of K and Kv2.1 channels to the plasma membrane. (bireme.br)
  • There are many types of potassium ion channels (voltage-gated K+ channels, ATP-sensitive K+ channels, Ca2+-activated K+ channels, etc.), and each type of potassium ion channel has its own characteristic features concerning electrophysiology and molecular biology in each potassium ion channel. (novapublishers.com)
  • To do this, we use a combination of quantitative behavioral analysis, genetics, in vivo electrophysiology, and heterologous expression of ion channels. (stanford.edu)
  • The BK-β1, encoded by the KCNMB1 gene, is a key determinant of BK channel electrophysiology. (diabetesjournals.org)
  • Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels. (wikipedia.org)
  • It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel. (wikipedia.org)
  • FLB-12 significantly inhibits the PXR-activated loss of righting reflex to 2,2,2-tribromoethanol (Avertin) in vivo, abrogates PXR-mediated resistance to 7-ethyl-10-hydroxycamptothecin (SN-38) in colon cancer cells in vitro, and attenuates PXR-mediated acetaminophen hepatotoxicity in vivo. (aspetjournals.org)
  • MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). (curehunter.com)
  • The large conductance calcium- and voltage-activated K + channel (BK, KCa1.1, MaxiK) channel is encoded by a single gene ( KCNMA1 , SLO-1 ). (frontiersin.org)
  • Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels (maxiK or BK channels) with high affinity (Kd ~1 nM). (wikipedia.org)
  • MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. (genecards.org)
  • RA-FLS express KCa1.1 (BK, Slo1, MaxiK, KCNMA1 ) as their major plasma membrane potassium channel. (biomedcentral.com)
  • To examine the effect of partial urethral obstruction (PUO) on bladder smooth muscle outward potassium current and the contribution of the large-conductance calcium-activated potassium (Maxi-K, BKCa) channel to this activity in smooth muscle cells isolated from bladders of sham-operated and PUO male rats using whole-cell patch clamp recording techniques. (elsevier.com)
  • Maxi-K+ channels (BKCa) play a significant role in modulating cell membrane potential and excitability.Objective: This study was designed to investigate the potential involvement of BKCa channel function in the response of human myometrium to beta(3)-adrenoceptor activation.Design: Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes were obtained in the presence and absence of BRL37344, a specific beta(3)-adrenoreceptor agonist. (nuigalway.ie)
  • The in vitro effects of BRL37344 on isolated myometrial contractions, in the presence and absence of the specific BKCa channel blocker, iberiotoxin ( IbTX), were investigated.Setting: The study was carried out at the Clinical Science Institute. (nuigalway.ie)
  • 0.05), and preincubation of these strips with IbTX attenuated this effect on both spontaneous and oxytocin- induced contractions (44.44 and 57.84% at 10(-5) M, respectively).Conclusions: These findings outline that activation of the BKCa channel may explain the potent uterorelaxant effect of beta(3)-adrenoreceptor agonists. (nuigalway.ie)
  • Inhibitors and activators were used to characterize the involvement of nitric oxide, soluble guanylate cyclase, cyclic GMP, protein kinase G and BKCa channel. (ufl.edu)
  • Exposure of trabecular meshwork cells to nitric oxide resulted in decreased cell volume and these decreases were abolished by ODQ and the BKCa channel inhibitor, IBTX, suggesting the involvement of soluble guanylate cyclase and K+ eflux respectively. (ufl.edu)
  • Because calcium-activated potassium (BKCa) channels are essential for vascular smooth muscle cell (VSMC) relaxation, we hypothesized that aldosterone alters their expression and/or function in VSMCs. (ahajournals.org)
  • BKCa channels may therefore be useful therapeutic targets in cardiovascular diseases. (ahajournals.org)
  • This co-localization to areas of high local calcium levels adds a regulatory level. (frontiersin.org)
  • Using voltage-clamp techniques, it is possible to study charge movement in the channel regulatory apparatus. (rupress.org)
  • Because of a high density in myocyte membranes and large conductance properties, BK Ca channels are an important determinant of vascular tone. (aspetjournals.org)
  • A Review by Faundez and Hartzell concerns the functions of intracellular chloride channels in endosomes and related organelles, concluding with an intriguing scenario whereby chloride channels in the membranes of synaptic vesicles could help determine their neurotransmitter content. (sciencemag.org)
  • BK channels can be activated by the increase of the intracellular Ca2+ concentration, a consequence of neuronal excitation, and then terminate the action potential with the outward K+ flux. (eurekaselect.com)
  • These effects are likely associated with the alterations in neuronal cell membrane ion channel activities. (biomedcentral.com)
  • Collectively, the results suggest that the IH-induced NO deficit mediated by a down-regulation of the expression of neuronal NO synthase plays a causative role in the impaired activity of BK channels, which could account for the hippocampal injury in patients with sleep apnea. (naver.com)
  • Consequently, the channel has many important physiological roles including regulation of smooth muscle tone, neurotransmitter release and neuronal excitability. (frontiersin.org)
  • BK channels are essential for the regulation of several key physiological processes including smooth muscle tone and neuronal excitability. (wikipedia.org)
  • Developmental regulation of neuronal K(Ca) channels by TGFbeta1: an essential role for PI3 kinase signaling and membrane insertion. (semanticscholar.org)
  • Developmental regulation of neuronal KCa channels by TGFbeta 1: transcriptional and posttranscriptional effects mediated by Erk MAP kinase. (semanticscholar.org)
  • Due to the significance of potassium channels in neuronal functions, the overexpression of this gene may play a role in the abnormal neurological functions seen in some of these patients. (tcdb.org)
  • Regulates the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. (abcam.com)
  • In response to these afferent inputs, neuronal pathways are activated that influence energy flux and nutrient metabolism in the body and ensure reproductive competency. (diabetesjournals.org)
  • Although higher calcium affinities might be found in other splice variants, these inconsistencies imply that native hair cell BK channels may contain other components that combine with and modify the slo-α gene product. (jneurosci.org)
  • We estimate the tuning frequencies for eight varieties of BK channel and predict the corresponding position of each gene product along the tonotopically organized basilar papilla of the chick. (jneurosci.org)
  • Factors altering the activity of BK channels, such as gene mutations, polymorphism, channel openers or blockers that lead to loss- or gain-of-function, have all been linked to epilepsy onset. (eurekaselect.com)
  • Maxi-K channel openers or gene therapy may therefore provide therapeutic benefit for the overactive bladder. (elsevier.com)
  • The mouse Slo3 gene (KCNMA3) encodes a K(+) channel that is regulated by changes in cytosolic pH. (semanticscholar.org)
  • Gene Ontology (GO) annotations related to this gene include potassium channel regulator activity and calcium-activated potassium channel activity . (genecards.org)
  • Chloride channel accessory 1 is a protein that in humans is encoded by the CLCA1 gene. (wikipedia.org)
  • This gene encodes a member of the calcium sensitive chloride conductance protein family. (wikipedia.org)
  • Association of seven renin angiotensin system gene polymorphisms with restenosis in patients following coronary stenting Percutaneous coronary intervention, despite being effective for coronary revascularization, causes in-stent restenosis due to neointimal hyperplasia in a large number of patients. (tripdatabase.com)
  • After a short introduction to the structure, function and regulation of BK channels, we review the small organic molecules activating BK channels and how these tool compounds have helped delineate the roles of BK channels in health and disease. (frontiersin.org)
  • Activity- and target-dependent regulation of large-conductance Ca2+-activated K+ channels in developing chick lumbar motoneurons. (semanticscholar.org)
  • This book will focus on the characteristics, function and regulation of several types of potassium ion channels, focusing on the role of these channels not only in terms of physical responses, but also in the aforementioned diseases. (novapublishers.com)
  • A K + channel whose regulation, at a basic level, is formulaically similar to that of hemoglobin (though mechanistically distinct), is the large-conductance voltage- and Ca 2+ -dependent (BK) channel. (rupress.org)
  • In 2006 I postulated that the AMP-activated protein kinase (AMPK), which is key to the cell autonomous regulation of metabolic homeostasis , might serve to regulate oxygen and thus energy (ATP) supply at the whole body as well as the cellular level. (ed.ac.uk)
  • In this study, we hypothesized that the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway plays a significant role in the regulation of coronary BK channel function and vasodilation in high-fat diet (HFD)-induced obese/diabetic mice. (diabetesjournals.org)
  • In this second Focus Issue in an ongoing series of articles on the regulation and function of ion channels, Science 's STKE presents four articles that highlight various aspects of ion channel function. (sciencemag.org)
  • Trauner and Kramer discuss various examples of metabolic regulation of potassium channels, speculating that other classes of potassium channels may be similarly subject to regulation by various small metabolites. (sciencemag.org)
  • The abolition of channel inactivation by alkaline phosphatase was prevented by prior internal tetraethylammonium treatment, indicating that the alkaline phosphatase site is closely associated with the channel pore. (dundee.ac.uk)
  • A K+ channel pore domain (S5, selectivity filter, and S6). (wikipedia.org)
  • The first is the conductance Hill energy W H [ g ] , which is a "local" work function for pore activation, and is defined as kT times the Hill transform of the conductance (G-V) curve. (rupress.org)
  • The main objective when analyzing equilibrium data are to identify elements that respond to external forces, and to quantify their interactions with the catalytic unit, which in ion channels is the conducting pore. (rupress.org)
  • The BK channel derives its voltage dependence from four voltage-sensing (J) domains located within the membrane electric field, and also to a small degree from the pore (L) itself. (rupress.org)
  • Activated channels open a pore across the cell membrane for selected ions, causing changes in the membrane potential and/or the intracellular concentration of ions such as Ca 2+ that serve as important cellular signals. (physiology.org)
  • In collaboration with Mike Zhu (University of Texas Medical School at Houston) we identified Two Pore Channels (TPCs) as a novel family of ion channels that are principally targeted to endolysosomes, and may be gated by cellular messengers such as, for example, the Ca 2+ mobilising messenger NAADP. (ed.ac.uk)
  • Previous single-channel studies have shown that Mg(2+) blocks the pore of BK channels in a voltage-dependent manner. (nih.gov)
  • We also found that the amount of protein comprising the pore of the K Atp channel in the dorsal root ganglia innervating hindlimbs whose femoral artery was ligated was significantly greater than that in the dorsal root ganglia innervating hindlimbs whose femoral arteries were freely perfused. (elsevier.com)
  • The large conductance Ca2+- and voltage-activated potassium (BK) channel is activated via two important cellular signaling mechanisms: increases in intracellular Ca2+ and membrane depolarization. (umaryland.edu)
  • Pallanck and Ganetzky, 1994 ) (~250 pS measured in symmetrical K + ), but also because it can be activated by Ca 2+ alone, membrane depolarization alone, or synergistically by both ( Magleby, 2003 ). (frontiersin.org)
  • Large conductance, voltage- and Ca 2+ -activated K + (BK Ca ) channels regulate blood vessel tone, synaptic transmission, and hearing owing to dual activation by membrane depolarization and intracellular Ca 2+ . (rupress.org)
  • We studied the electrophysiological behavior of Purkinje cells in genetically engineered alert mice that do not express BK calcium-activated potassium channels and in wild-type mice with pharmacological BK inactivation. (biomedsearch.com)
  • Molecular, biophysical, and pharmacological properties of calcium-activated chloride channels. (bireme.br)
  • In this chapter we discuss the data obtained for a calcium-activated potassium channel of large unitary conductance. (springer.com)
  • In fact, resveratrol has been reported to regulate ion channel activities in a variety of cells. (biomedcentral.com)
  • Healthy cerebrovascular myocytes express members of several different ion channel families which regulate resting membrane potential, vascular diameter, and vascular tone and are involved in cerebral autoregulation. (hindawi.com)
  • NMDA receptors mediate leptin signaling and regulate potassium channel trafficking in pancreatic -cells. (bireme.br)
  • The ability of NMDARs to regulate potassium channel surface expression and thus, -cell excitability provides mechanistic insight into the recently reported insulinotropic effects of NMDAR antagonists and therefore highlights the therapeutic potential of these drugs in managing type 2 diabetes. (bireme.br)
  • In contrast, mechanisms that regulate channel surface expression in native cell types, including arterial myocytes, are unclear. (physiology.org)
  • These findings are consistent with a model in which IL-4 rapidly increases near-membrane calcium concentrations to regulate BK(Ca) activity. (umassmed.edu)
  • Key to our hypothesis was the proposal that AMPK might directly phosphorylate and regulate ion channel complexes and thus mediate the activities of those oxygen-sensing cells that underpin each of these processes. (ed.ac.uk)
  • A patient with severe infection of staphylococcus aureus acquired completely spontaneous remission (SR), moreover a increased number of pDC were observed, suggesting that bacteria-activated pDC may play an important role in SR. This study was purposed to explore if the bacteria can stimulate pDC successfully and get a functional pDC. (jove.com)
  • Thus, HBSMC contain functional BK(Ca) channels whose activity is rapidly potentiated by the cytokine, IL-4, but not by IL-13. (umassmed.edu)
  • Patch fluorometry has emerged as a new approach to the study of the structure-function relationship in membrane-embedded functional ion channels. (physiology.org)
  • The power of patch fluorometry comes from this ability to directly correlate a structural change to its functional effect on channel activity. (physiology.org)
  • Its introduction to functional channels in the intact membrane environment, however, occurred only recently. (physiology.org)
  • Kinetic properties of membrane transporters are typically poorly defined because high-resolution functional assays analogous to single-channel recordings are lacking. (sciencemag.org)
  • Nerve-evoked relaxations of precontracted strips were reduced by 50%, both in strips from Slo-/- mice and by blocking BK channels with iberiotoxin in the Slo+/+ strips. (nih.gov)
  • Iberiotoxin (300 nM) sensitive Maxi-K channel current comprised about 40% of the outward whole-cell current in SHAM bladders but only about 8% in PUO bladders. (elsevier.com)
  • BK channels are blocked by tetraethylammonium (TEA), paxilline and iberiotoxin. (wikipedia.org)
  • Iberiotoxin (IbTX) is an ion channel toxin purified from the Eastern Indian red scorpion Buthus tamulus. (wikipedia.org)
  • We tested the likelihood of this explanation by measuring the effects of either glibenclamide (0.1 mg/kg), which blocks K Atp channels, or iberiotoxin (20 or 40 (μg/kg), which blocks BK Ca channels, on the tempol-induced attenuation of the exercise pressor and muscle mechanoreceptor reflexes in decerebrated rats whose femoral arteries were ligated. (elsevier.com)
  • After iberiotoxin, relaxation to acetylcholine was decreased to a larger extent in male wild-type than in MAS, leading to similar levels of relaxation. (ahajournals.org)
  • Intracellular Ca2+ (Ca2+i) is required for BK channel activation and previous studies have shown BK current is predominantly coupled to two types of Ca2+ sources in the SCN: L-type Ca2+ channels (LTCCs), and ryanodine receptors (RyRs). (umaryland.edu)
  • Slo1 BK channels are thus receptors for long-chain omega-3 fatty acids, and these fatty acids-unlike their ethyl ester derivatives-activate the channels and lower blood pressure. (pnas.org)
  • Their mechanism of action in tocolysis involves the blockade of L-type Ca 2+ channels, influenced by the Ca 2+ -activated K + channels, beta-adrenergic receptors (β-ARs) and sexual hormones. (mdpi.com)
  • NMDA receptors (NMDARs) are Ca -permeant, ligand-gated ion channels activated by the excitatory neurotransmitter glutamate and have well-characterized roles in the nervous system. (bireme.br)
  • Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1, GALR2, and GALR3. (uniprot.org)
  • Next, to determine which Ca2+ channels are involved in Ca2+i rhythms, this study tested the effects of the same Ca2+ channel pharmacology on the circadian parameters of Ca2+i measured from SCN slice cultures transfected with a fluorescent Ca2+ sensor. (umaryland.edu)
  • The pharmacology and molecular biology of large-conductance calcium-activated (BK) potassium channels. (semanticscholar.org)
  • Na+ ions were not measurably permeant through the open channel. (edu.au)
  • The BK channel was inhibited reversibly by external tetraethylammonium (TEA) ions, charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and apamin. (edu.au)
  • Moreover, the protein kinase, Akt, can be activated by various growth factors and its activity can be blocked by PTEN. (sigmaaldrich.com)
  • One of my primary areas of research is the role of -activated protein kinase in mediating chemotrasduction by hypoxia in oxygen-sensing cells. (ed.ac.uk)
  • BK channels modulate neurotransmitter release due to their activation by voltage and Ca(2+). (nih.gov)
  • Considering this negative feedback effect, BK channel seemly acts to decrease membrane excitability in order to prevent hyperexcitation which is a typical characteristic of epilepsy. (eurekaselect.com)
  • Conclusion: The aim of this review is to summarize existing knowledge and recent findings on the molecular properties, signaling complex and channel dysfunction of the BK channels with a particular attention to the possible relevance to the pathophysiology of epilepsy. (eurekaselect.com)
  • The potassium ion current across the plasma membrane is considered to have two main physiological functions, one for determining the membrane potential and the other regulating the electrical activity. (novapublishers.com)
  • Therefore, potassium ion channels show the physiological effects in each tissue via membrane potential mediated Ca2+ dynamics (for example, excitation-contraction coupling in muscle). (novapublishers.com)
  • Knowledge of channel structures as well as dynamic changes in these structures is crucial to fully understand how an ion channel works under normal physiological conditions and how channel functions are affected under pathological conditions. (physiology.org)
  • Quantitative computation of these effects reveals that the overall effect of Mg(2+) under physiological conditions is to enhance BK channel function. (nih.gov)
  • The resonant frequency is determined in large part by the number and kinetics of large conductance, calcium-activated potassium (BK) channels. (jneurosci.org)
  • Deactivation kinetics were used to predict tuning frequencies and thus tonotopic location if hair cells were endowed with each of the expressed channels. (jneurosci.org)
  • Electrical tuning frequencies vary systematically (tonotopically) along the turtle's basilar papilla ( Crawford and Fettiplace, 1980 ), leading to the remarkable conclusion that the molecular determinants of BK channel kinetics must be tonotopically distributed as well. (jneurosci.org)
  • These results indicate that the BK channel has an important role in erectile function, and loss of the BK channel leads to erectile dysfunction. (nih.gov)
  • Sleep apnea associated with chronic intermittent hypoxia (IH) impairs hippocampal functions but the pathogenic mechanisms involving dysfunction of nitric oxide (NO) and ionic channels remain unclear. (naver.com)
  • Calcium signaling plays a central role in normal CNS functioning and dysfunction. (biomedsearch.com)
  • We conclude that EDPs potently dilate coronary microvessels and are the most potent fatty epoxides known to activate BK Ca channels in coronary smooth muscle cells. (aspetjournals.org)
  • Early animal studies suggested that EETs hyperpolarized vascular smooth muscle cells through activation of BK Ca channels ( Hu and Kim, 1993 ). (aspetjournals.org)
  • Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is decreased in urinary bladder smooth muscle cells from male rats with partial urethral obstruction. (elsevier.com)
  • Our findings show that obstruction of the rat bladder is associated with decreased Maxi-K channel activity of bladder smooth muscle cells, determined via direct current measurement. (elsevier.com)
  • Fingerprint Dive into the research topics of 'Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is decreased in urinary bladder smooth muscle cells from male rats with partial urethral obstruction. (elsevier.com)
  • In vascular smooth muscle cells, large-conductance Ca 2+ - and voltage-activated K + (BK) channels provide a critical vasodilatory influence. (pnas.org)
  • Because vasospastic smooth muscle cells are known to be depolarized compared to controls [ 3 , 4 ], the expression and function of ion channels in these cells after SAH are of great interest. (hindawi.com)
  • Membrane potential of cerebrovascular smooth muscle cells and thus dilation and constriction of cerebral arteries are directly dependent on potassium conductance [ 5 , 6 ]. (hindawi.com)
  • The large-conductance, voltage-gated, calcium (Ca 2+ )-activated potassium channel (BK Ca ) plays an important role in regulating the membrane potential of uterine muscle cells. (pnas.org)
  • Furthermore, we report that activated α 2 M regulates BK Ca activity and that activated α 2 M and BK Ca together control Ca 2+ oscillations in the cells, a process dependent on store-operated Ca 2+ entry. (pnas.org)
  • Since the Cl flow into or out of the cell plays a crucial role in hyperpolarizing or depolarizing the cells, respectively, the impact of intracellular Ca concentration on these channels is attracting a lot of attentions. (bireme.br)
  • On the other hand, the modification of potassium ion channel activity would be expected to have a significant effect on the excitability of various cells. (novapublishers.com)
  • Previous studies have focused primarily on identifying mechanisms that control plasma membrane (surface) BK channel activity in cells. (physiology.org)
  • Large-conductance, calcium-activated potassium (BK(Ca)) channels are regulated by voltage and near-membrane calcium concentrations and are determinants of membrane potential and excitability in airway smooth muscle cells. (umassmed.edu)
  • Large conductance calcium-activated potassium channels (BK Ca ) are abundantly expressed in smooth muscle cells (SMCs) lining the blood vessel wall. (ahajournals.org)
  • Ion channels are cellular sensors allowing cells to respond to a wide spectrum of stimuli that are either physical (e.g., membrane potential, mechanical force, temperature) or chemical (e.g., neurotransmitters, second messengers) in nature ( 15 ). (physiology.org)
  • Site-specific cysteine mutagenesis, for example, is a simple way to generate such a docking site in cloned channels expressed in cultured cells. (physiology.org)
  • A traditional cell-free, inside-out, patch-clamping configuration is established from cells expressing these channels. (physiology.org)
  • Thus, in vivo, it is possible that dilation is larger, and some of the effect of CO 2 on cerebral vessels is mediated by extravascular cells. (asahq.org)
  • Diabetes is closely associated with increased risks of cardiovascular diseases, which are the leading cause of death in the U.S. The large-conductance calcium-activated potassium (BK) channels are abundantly expressed in coronary arterial smooth muscle cells (SMCs), playing an important role in regulating coronary circulation and myocardial perfusion ( 1 - 4 ). (diabetesjournals.org)
  • These results demonstrate that cortical large-conductance calcium-activated potassium channel inactivation is probably mediated by an endogenous, trypsin-sensitive, inactivation particle. (dundee.ac.uk)
  • PA relaxation was dependent of the large conductance calcium-activated potassium channel (BK Ca ). JAK2 inhibition activated BK Ca channels and reduced intracellular Ca 2+ . (bmj.com)
  • Furthermore, it showed dose-dependent vasodilator activity in aortic rings in the presence of endothelium, whose hypotensive mechanism is partially mediated by nitric oxide synthase/guanylate cyclase and large-conductance calcium-dependent potassium channels. (hindawi.com)
  • Conversely, activation of NMDARs mimicked the effect of leptin, causing Ca influx, AMPK activation, and increased trafficking of K and Kv2.1 channels to the plasma membrane, and triggered membrane hyperpolarization. (bireme.br)
  • Here we investigate β4's effect on BK channel trafficking to the plasma membrane. (pubmedcentralcanada.ca)
  • Calcium-activated chloride channels (CaCCs) are a family of anionic transmembrane ion channels. (bireme.br)
  • Intracellular Mg(2+) also modulates BK channels in multiple ways with opposite effects on channel function. (nih.gov)
  • Vascular endothelium contains cytochrome P-450 epoxygenases that transform the n -6 fatty acid arachidonate into epoxyeicosatrienoic acids (EETs), potent dilators of coronary arterioles and activators of large-conductance calcium-activated potassium (BK Ca ) channels. (aspetjournals.org)
  • Activation of BK channels hyperpolarizes the membrane potentials of vascular SMC, leading to the reduction of intracellular Ca 2+ concentration and vascular relaxation. (diabetesjournals.org)
  • However, in response to increased oxidative stress, the vascular BK channel function is impaired, with reduced BK-β1 protein expression being a common feature in the vascular SMCs of prediabetic, type 1 diabetic, and type 2 diabetic animals ( 8 - 13 ). (diabetesjournals.org)
  • Here, changes in calcium and potassium channel expression and function in animal models of subarachnoid hemorrhage and transient global ischemia are systematically reviewed and their clinical significance discussed. (hindawi.com)
  • the molecular process of how Ca 2+ binding is coupled to channel opening has been less studied. (rupress.org)
  • Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown. (bmj.com)
  • C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels. (semanticscholar.org)
  • BK channels have also been found to be activated by exogenous pollutants and endogenous gazotransmitters carbon monoxide and hydrogen sulphide. (wikipedia.org)
  • n = 5) BK Ca channels in myocytes from the porcine coronary arterioles. (aspetjournals.org)
  • May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. (genecards.org)
  • Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations. (genecards.org)
  • Here we examine the origins of kinetic variability among BK channels by heterologous expression of avian cochlear slo cDNAs. (jneurosci.org)
  • In animal models, in response to subarachnoid blood, a dynamic transition of ion channel expression and function is initiated, with acute and long-term effects differing from each other. (hindawi.com)
  • Initial hypoperfusion after exposure of cerebral vessels to oxyhemoglobin correlates with a suppression of voltage-gated potassium channel activity, whereas delayed cerebral vasospasm involves changes in other potassium channel and voltage-gated calcium channels expression and function. (hindawi.com)
  • The goal of the present analysis is to review ion channel expression and function in healthy cerebral blood vessels as well as after SAH. (hindawi.com)
  • It remains to be determined if BK channels contribute to intoxication in humans. (wikipedia.org)
  • It is, however, difficult to design large scale experiments in humans to verify causal roles for these candidate genes. (biomedcentral.com)
  • One important target of PKGI in smooth muscle is the large-conductance, calcium-activated potassium (BK) channel, which upon activation hyperpolarizes the smooth muscle cell membrane, causing relaxation. (nih.gov)
  • The channel activation by Ca(2+) became more cooperative by the coexpression of rbeta4. (nih.gov)
  • Ligand-dependent activation of Slo family channels is defined by interchangeable cytosolic domains. (semanticscholar.org)
  • Caspase-8 activation can also activate Bid, leading to activation of the apoptotic program. (sigmaaldrich.com)
  • Alternatively, Akt activates IKK-α that ultimately leads to NF-κB activation and cell survival. (sigmaaldrich.com)
  • Nevertheless, the proposed mechanism of MthK activation based on its structure provides an excellent model for this aspect of BK Ca channel activation. (rupress.org)
  • BK ‐channels are Ca 2+ ‐activated large‐conductance K + ‐channels that require close proximity to Ca 2+ ‐channels for activation and control Ca 2+ ‐triggered neurotransmitter release by accelerating membrane repolarization during action potential firing. (embopress.org)
  • For example, using two different fluorescence resonance energy transfer (FRET) approaches, Bezanilla and colleagues ( 4 , 33 ) recently demonstrated that a limited transmembrane movement of the S4 voltage sensor is sufficient to drive the activation of Shaker channels. (physiology.org)
  • This mechanism of cooperative Mg2+ binding is described by the model for allosteric transitions (Fig. 1), which is similar to the mechanism of Ca2+-dependent activation of the channel (Cox et al. (nih.gov)
  • Patch-clamp studies showed that coronary BK-β1-mediated channel activation was diminished in HFD mice. (diabetesjournals.org)
  • Importantly, the activation of Nrf2 by dimethyl fumarate significantly reduced the body weight and blood glucose levels of HFD mice, enhanced BK-β1 transcription, and attenuated MuRF1-dependent BK-β1 protein degradation, which in turn restored coronary BK channel function and BK channel-mediated coronary vasodilation in HFD mice. (diabetesjournals.org)
  • In addition, the NF-κB/p65 can be directly activated by reactive oxygen species (ROS) through phosphorylation of NF-κB/p65 ( 15 ). (diabetesjournals.org)
  • RBP 1,2 double knockout mice show impaired presynaptic localization of BK α‐channel protein. (embopress.org)
  • Our results indicated that the attenuation of action potential firing rate by resveratrol might be mediated through opening the BK Ca channels and closing the voltage-gated sodium channels. (biomedcentral.com)
  • The slow time-course of channel inactivation may have some pathophysiological significance in maintenance of epileptiform activity. (dundee.ac.uk)
  • An alternative explanation for the tempol-induced attenuation of these reflexes involves ATP-sensitive potassium channels (K Atp ) and calcium-activated potassium channels (BK Ca ), both of which are opened by tempol. (elsevier.com)