Aim Endothelial cell (EC) KCa2.3 and KCa3.1, calcium-activated potassium channels, play a crucial role in NO- and EDHF-mediated regulation of vascular tone by controlling membrane potential and intracellular calcium levels. Since laminar shear stress (LS) is a major determinant of EC function in a calcium-dependent manner, we hypothesized that LS upregulates KCa2.3 and KCa3.1 via activating calcium/calmodulin (CaM) kinase cascade.. Methods Human coronary artery ECs were exposed to static, LS (15 dyn/cm2) or oscillatory shear stress (OS; +/−5 dyn/cm2 × 1Hz) condition for 24 hours in the absence or presence of STO-609 (CaM-dependent kinase kinase (CaMKK) inhibitor, 10μg/ml), Compound C (AMP-activated protein kinase (AMPK) inhibitor, 10μM), KN-62 (calcium/CaM-dependent kinase (CaMK) inhibitor, 10μM), KG-501 (cAMP response element binding protein (CREB) inhibitor, 25μM), or tumor necrosis factor-α (TNF-α; 1 or 10 ng/ml). The mRNA expression and CREB phosphorylation were determined by ...
Calcium management differs in T and B lymphocytes. [Ca2+]i elevation in response to calcium ionophores is up to 10 times greater in T cells than B cells. There is no difference between them in ionophore uptake. T cells, but not B cells, possess a calcium-sensitive potassium channel which produces membrane hyperpolarization at [Ca2+]i above 200 nM. This alters T cell density providing a rapid and easy method of cell separation. In contrast, B cells depolarize when [Ca2+]i is increased. Isolated B cell membrane vesicle ATP-dependent calcium pump activity is higher than T cell vesicles. Membrane depolarization reduces the [Ca2+]i response to ionomycin, most dramatically in T cells because they are hyperpolarized by increased [Ca2+]i. The most likely basis of this behavior is an effect of membrane potential on lymphocyte membrane calcium pump activity. This mechanism provides an explanation of the inhibitory effect of membrane depolarization on T lymphocyte responses. ...
Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene is a member of the KCNN family of potassium channel genes. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013 ...
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin (By similarity).
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
[ChEMBL Target Description] ID:CHEMBL3381, Name:Small conductance calcium-activated potassium channel protein 3, Description:, Synonyms:
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri (A.D.W.); Departments of Microbiology and Molecular Genetics (G.A.G.) and Physiology and Biophysics (K.G.C.), University of California, Irvine, Irvine, California; Molecular and Cellular Physiology Department, Stanford University, Stanford, California (R.A.); Department of Medical Pharmacology and Toxicology, University of California, Davis, Davis, California (H.W.); and Department of Applied Physiology, University Ulm, Ulm, Germany (S.G.) ...
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
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. ...
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 ...
annotations (the reliablity of the annotated protein expression using immunohistochemically (IH) stained on human tissues, the reliablity of the annotated protein expression in immunofluorescently (IF) stained human cell lines, tissue specificity (the distribution of antibody staining or protein expression in human cell types), cell line specificity (the distribution of RNA abundance in cell lines) and subcellular location (based on immunofluorescent staining of cell lines ...
Summary is not available for the mouse gene. This summary is for the human ortholog.] 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, which is the product of this gene, and the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008 ...
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 ...
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 ...
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 ...
Characterisation and interaction between β₂ adrenoceptor (AR) and the large conductance calcium-activated potassium (BK_C_a) channel in human myometrium during pregnancy ...
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,
Summary is not available for the mouse gene. This summary is for the human ortholog.] Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. This gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel, which is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene contains two CAG repeat regions in the coding sequence. It was thought that expansion of one or both of these repeats could lead to an increased susceptibility to schizophrenia or bipolar disorder, but studies indicate that this is probably not the case. Alternatively spliced transcript variants encoding different isoforms have ...
KCNN4 antibody (potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4) for ELISA, WB. Anti-KCNN4 pAb (GTX87069) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
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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 ...
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anti-Potassium Large Conductance Calcium-Activated Channel, Subfamily M, beta Member 1 (KCNMB1) antibody (Alexa Fluor 647) ABIN903516 from antibodies-online
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 ...
K+ channel expression and function is closely related to vascular smooth muscle cell (SMC) phenotype. Large conductance Ca2+-activated K+ channels (BKCa) control excitation-contraction coupling and predominate in SMCs with a contractile phenotype1. Intermediate conductance Ca2+-activated K+ channels (IKCa) regulate proliferation during vasculogenesis and are expressed in SMCs with an immature or synthetic phenotype1. We previously demonstrated fetoplacental arterial SMCs have a mixed phenotype and express both contractile and synthetic proteins2. Here we test the hypothesis that SMCs isolated from fetoplacental arteries express BKCa and IKCa channels. SMCs were isolated from chorionic plate arteries of normal term placentas using methods reported previously1. Whole-cell patch clamp was used to assess K+ currents, (5mM [K+]e, 140mM [K+]i, 0.5mM EGTAi, 0mM [ATP]i). Cells were clamped at -60mV and depolarised from -70mV to +80mV for 500ms to record current-voltage relationships. KCa channel ...
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
Our results obtained from humans demonstrate that KCa channels are involved in regulation of the mechanical properties of peripheral conduit arteries, supporting a role for EDHF at this level in vivo. In addition, the synergistic effect of l-NMMA and TEA on radial artery constriction and arterial wall stiffening in absence of such effects after administration of l-NMMA alone shows that KCa channels compensate for the loss of NO synthesis to maintain peripheral conduit artery diameter and mechanics.. The present study was performed in healthy subjects at the level of the radial artery to assess in vivo the role of NO and vascular KCa channels and their potential interaction in the regulation of basal conduit artery diameter and mechanics. All experiments were performed after administration of aspirin to inhibit vascular cyclooxygenase and to exclude a role for PGI2 in our results.15,24 The inhibition of endothelial NO synthesis was obtained with l-NMMA, infused at a dose of 8 μmol/min, known to ...
TY - JOUR. T1 - SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines. AU - Ngo-Anh, Thu Jennifer. AU - Bloodgood, Brenda L.. AU - Lin, Michael. AU - Sabatini, Bernardo L.. AU - Maylie, James. AU - Adelman, John. PY - 2005/5. Y1 - 2005/5. N2 - Small-conductance Ca2+-activated K+ channels (SK channels) influence the induction of synaptic plasticity at hippocampal CA3-CA1 synapses. We find that in mice, SK channels are localized to dendritic spines, and their activity reduces the amplitude of evoked synaptic potentials in an NMDA receptor (NMDAR)-dependent manner. Using combined two-photon laser scanning microscopy and two-photon laser uncaging of glutamate, we show that SK channels regulate NMDAR-dependent Ca2+ influx within individual spines. SK channels are tightly coupled to synaptically activated Ca2+ sources, and their activity reduces the amplitude of NMDAR-dependent Ca2+ transients. These effects are mediated by a feedback loop within the spine head; during ...
Drosophila nociceptive neurons convert high-intensity stimuli into characteristic fluctuations of firing rates, quiescent periods of which are regulated by hyperpolarization through small conductance Ca2+-activated K+ channels.
How is intermediate-conductance K+ channel abbreviated? i-K+ stands for intermediate-conductance K+ channel. i-K+ is defined as intermediate-conductance K+ channel rarely.
The purpose of the present study was to examine how apamin interacts with the three cloned subtypes of small-conductance Ca2+-activated K+ channels (hSK1, rSK2 and rSK3). Expression of the SK channel subtypes in Xenopus laevis oocytes resulted in large outward currents (0.5-5 microA) after direct in …
Endothelial cell, Ca2+-activated K channels (SKCa and IKCa channels) generate hyperpolarization that passes to the adjacent vascular smooth muscle cells to cause vasodilation in small resistance arterioles. IKCa channels expressed within endothelial cell projections toward the SMCs are activated by spontaneous Ca2+ events (Ca2+ puffs/pulsars). TRPV4 channels also cluster within this microdomain and are selectively activated at low intravascular pressure resulting in activation of endothelial cell IKCa channels and vasodilation, reducing the myogenic tone that underpins tissue blood-flow autoregulation. ...
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 ...
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.
4J9Z: Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca2+-sensing and SK channel activation.
Background: Large-conductance, calcium-activated potassium (Maxi-K) channels are implicated in the modulation of human uterine contractions and myometrial Ca2+ homeostasis. However, the regulatory mechanism(s) governing ...
KCNN3兔多克隆抗体(ab28631)可与人样本反应并经WB, ELISA实验严格验证,被1篇文献引用。所有产品均提供质保服务,中国75%以上现货。
Our results demonstrate that maxi-K channels in smooth muscle cells are regulated by agents that alter the redox state of sulfhydryl groups. We have shown that sulfhydryl reduction increases nPo of the channel whereas oxidation has the opposite effect. Maxi-K channels in patches pulled from smooth muscle cells appear to exist in a mixed redox state, since either reduction or oxidation markedly affected channel activity. This mixed redox state could occur either because some channels in the patch exist in the reduced state whereas others are in the oxidized state, or because each channel has more than one redox modulatory site existing in different redox states. Since membrane patches from airway myocytes always contain multiple channels, we could not differentiate between these two possibilities.. We compared the normalized conductance-voltage curves constructed from macroscopic currents in response to step-depolarization during control and after sulfhydryl reduction to determine whether ...
BACKGROUND Accumulating data point to intermediate-conductance calcium-activated potassium channel (IKCa1) as a key player in controlling cell cycle progression and proliferation of human cancer cells. However, the role that IKCa1 plays in the growth of human cervical cancer cells is largely unexplored. MATERIAL AND METHODS In this study, Western blot analysis, immunohistochemical staining, and RT-PCR were first used for IKCa1protein and gene expression assays in cervical cancer tissues and HeLa cells. Then, IKCa1 channel blocker and siRNA were employed to inhibit the functionality of IKCa1 and downregulate gene expression in HeLa cells, respectively. After these treatments, we examined the level of cell proliferation by MTT method and measured IKCa1 currents by conventional whole-cell patch clamp technique. Cell apoptosis was assessed using the Annexin V-FITC/Propidium Iodide (PI) double-staining apoptosis detection kit. RESULTS We demonstrated that IKCa1 mRNA and protein are preferentially expressed
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 - Expression of intermediate-conductance, Ca2+-activated K+ channel (KCNN4) in H441 human distal airway epithelial cells. AU - Wilson, Stuart M.. AU - Brown, Sean G.. AU - McTavish, Niall. AU - McNeill, R. P.. AU - Husband, E. M.. AU - Inglis, Sarah K.. AU - Olver, Richard E.. AU - Clunes, M. T.. PY - 2006/6/9. Y1 - 2006/6/9. N2 - Electrophysiological studies of H441 human distal airway epithelial cells showed that thapsigargin caused a Ca2+-dependent increase in membrane conductance (GTot) and hyperpolarization of membrane potential (Vm). These effects reflected a rapid rise in cellular K+ conductance (GK) and a slow fall in amiloride-sensitive Na+ conductance (GNa). The increase in GTot was antagonized by Ba2+, a nonselective K+ channel blocker, and abolished by clotrimazole, a KCNN4 inhibitor, but unaffected by other selective K+ channel blockers. Moreover, 1-ethyl-2-benzimidazolinone (1-EBIO), which is known to activate KCNN4, increased GK with no effect on GNa. RT-PCR-based ...
Biological membranes, defining the boundary of cells and eukaryotic organelles, are mainly composed of lipids and membrane proteins. Interactions between these lipids and proteins are needed to preserve the tight seal of the membrane, but also to induce structure for proper function in many membrane proteins. In this thesis, interactions between three different kinds of peptides, i.e. small proteins, and model membranes are studied by spectroscopic methods.. First, the membrane interaction of two paddle domains, KvAPp, from the voltage-gated potassium channel KvAP from Aeropyrum pernix, and HsapBKp, from the human, large conductance, calcium-activated potassium channel HsapBK, was studied (paper I and II). In paper I, a high-resolution solution NMR structure of HsapBKp in detergent micelles is presented revealing a helix-turn-helix motif. Small structural differences between HsapBKp and KvAPp, positioning the arginines differently, are presented. These structural differences may explain why BK ...
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 ...
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
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 ...
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MMPokerNab: https://i.imgur.com/NLsxM.jpg While I discovered StarCraft Broodwar back in 2008, it seems people found online poker. And while I spent my time
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 ...
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
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