TY - JOUR. T1 - ATP sensitive potassium channel openers. T2 - A new class of ocular hypotensive agents. AU - Roy Chowdhury, Uttio. AU - Dosa, Peter I.. AU - Fautsch, Michael P. PY - 2016/3/2. Y1 - 2016/3/2. N2 - ATP sensitive potassium (KATP) channels connect the metabolic and energetic state of cells due to their sensitivity to ATP and ADP concentrations. KATP channels have been identified in multiple tissues and organs of the body including heart, pancreas, vascular smooth muscles and skeletal muscles. These channels are obligatory hetero-octamers and contain four sulfonylurea (SUR) and four potassium inward rectifier (Kir) subunits. Based on the particular type of SUR and Kir present, there are several tissue specific subtypes of KATP channels, each with their own unique set of functions. Recently, KATP channels have been reported in human and mouse ocular tissues. In ex vivo and in vivo model systems, KATP channel openers showed significant ocular hypotensive properties with no appearance of ...
Shop Probable potassium channel protein ELISA Kit, Recombinant Protein and Probable potassium channel protein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
TY - JOUR. T1 - The Role of the Voltage-Gated Potassium Channel Proteins Kv8.2 and Kv2.1 in Vision and Retinal Disease. T2 - Insights from the Study of Mouse Gene Knock-Out Mutations. AU - Hart, Nathan S. AU - Mountford, Jessica K. AU - Voigt, Valentina. AU - Fuller-Carter, Paula. AU - Barth, Melanie. AU - Nerbonne, Jeanne M. AU - Hunt, David M. AU - Carvalho, Livia S. PY - 2019/2. Y1 - 2019/2. N2 - Mutations in the KCNV2 gene, which encodes the voltage-gated K+ channel protein Kv8.2, cause a distinctive form of cone dystrophy with a supernormal rod response (CDSRR). Kv8.2 channel subunits only form functional channels when combined in a heterotetramer with Kv2.1 subunits encoded by the KCNB1 gene. The CDSRR disease phenotype indicates that photoreceptor adaptation is disrupted. The electroretinogram (ERG) response of affected individuals shows depressed rod and cone activity, but what distinguishes this disease is the supernormal rod response to a bright flash of light. Here, we have utilized ...
Title: Targeting Potassium Channels: New Advances in Cardiovascular Therapy. VOLUME: 3 ISSUE: 2. Author(s):Ramon Martinez-Marmol, Meritxell Roura-Ferrer and Antonio Felipe. Affiliation:Molecular Physiology Laboratory, Departament de Bioquimica i Biologia Molecular, Universitat de Barcelona, E-08028 Barcelona, Spain.. Keywords:Potassium channels, cardiovascular therapy, channelopathy, long QT syndrome, arrithmiogenesis, heart diseases. Abstract: Potassium channels, which are essential to a wide range of physiological processes, are involved in many diseases. Thus, alterations in such important proteins due to congenital deficiencies or to undesirable side-effects of common medications might lead to dysfunctions. Heart is one of those tissues where potassium channels play a crucial role. The maintenance of cardiac action potential appears to be the consequence of the varied activity of several types of potassium channels. Recently, compounds that modify cardiac potassium channel activity and so ...
TY - JOUR. T1 - Blockade of ATP-sensitive potassium channels prevents the attenuation of the exercise pressor reflex by tempol in rats with ligated femoral arteries. AU - Yamauchi, Katsuya. AU - Stone, Audrey J.. AU - Stocker, Sean D.. AU - Kaufman, Marc P.. PY - 2012/8/1. Y1 - 2012/8/1. N2 - We reported previously that tempol attenuated the exercise pressor and muscle mechanoreceptor reflexes in rats whose femoral arteries were ligated, whereas tempol did not attenuate these reflexes in rats whose femoral arteries were freely perfused. Although the mechanism whereby tempol attenuated these reflexes in rats whose femoral artery was ligated was independent of its ability to scavenge reactive oxygen species, its nature remains unclear. 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. We tested the likelihood of this explanation by ...
Potassium ion (K+) channels are ubiquitous components and are widely distributed on the surface of the cell membrane in various tissues. 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. 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. Membrane hyperpolarization would reduce the excitability of the membrane by shifting the membrane potential away from the threshold for excitation and would inhibit, where it existed, calcium ion (Ca2+) influx through voltage-gated Ca2+ channels by closing the Ca2+ channel. Outward potassium ion currents activated upon depolarization would counteract the depolarizing action ...
Carr DB, McDonnell Moorehead T, Bouchard A, et al. Effects of injectable HPβCD-diclofenac on the human delayed rectifier potassium channel current in vitro and on proarrhythmic QTc in vivo. Clin Ther. 2013;35(5):646-658. doi:10.1016/j.clinthera.2013.03.014. View article
TY - JOUR. T1 - Squaring the Circle. T2 - A New Study of Inward and Outward-Rectifying Potassium Currents in U251 GBM Cells. AU - Ratto, Daniela. AU - Ferrari, Beatrice. AU - Roda, Elisa. AU - Brandalise, Federico. AU - Siciliani, Stella. AU - De Luca, Fabrizio. AU - Priori, Erica Cecilia. AU - Di Iorio, Carmine. AU - Cobelli, Filippo. AU - Veneroni, Paola. AU - Bottone, Maria Grazia. AU - Rossi, Paola. PY - 2020/7. Y1 - 2020/7. N2 - In the present study, the functional role of the inwardly rectifying K+ channel, Kir4.1, and large-conductance Ca2+-activated K+ (BK) channel during cell migration in U251 cell line was investigated. We focused on polarised cells which are positive for the active-Cdc42 migration marker. The perforated patch technique was used to avoid intracellular dialysis and to maintain physiological changes in intracellular calcium. Wound healing was employed to assay migration after 24 h. Polarised cells recorded displayed different hallmarks of undifferentiated glial cells: ...
Transient exposure to ethanol (EtOH) results in a massive neurodegeneration in the developing brain leading to behavioral and cognitive deficits observed in fetal alcohol syndrome. There is now compelling evidence that K+ channels play an important role in the control of programmed cell death. The aim of the present work was to investigate the involvement of K+ channels in the EtOH-induced cerebellar granule cell death and/or survival. At low and high concentrations, EtOH evoked membrane depolarization and hyperpolarization, respectively. Bath perfusion of EtOH (10 mM) depressed the I(A) (transient K+ current) potassium current whereas EtOH (400 mM) provoked a marked potentiation of the specific I(K) (delayed rectifier K+ current) current. Pipette dialysis with GTPgammaS or GDPbetaS did not modify the effects of EtOH (400 mM) on both membrane potential and I(K) current. In contrast, the reversible depolarization and slowly recovering inhibition of I(A) induced by EtOH (10 mM) became irreversible in the
Most information currently available regarding vascular K+ channel function in diabetes concerns KATP channels. As for chronic hypertension, there are now several reports of impaired vascular relaxant responses to synthetic openers of KATP channels in long-term diabetes. These studies have mostly utilized the streptozotocin-injected rat model of diabetes and have examined vessels at 2.5 to 4 months after streptozotocin treatment. In this model in which plasma glucose levels are increased 3- to 4-fold, impaired relaxation of the isolated aorta122 123 124 and mesenteric vascular bed125 and reduced dilatation of large126 and small127 cerebral arteries in vivo typically develop. These changes are thought to be the result of a decreased number of vascular KATP channels and/or reduced sensitivity of these channels to synthetic openers. Nonspecific cytotoxic effects of streptozotocin seem an unlikely cause of these changes because, like other manifestations of vascular dysfunction, abnormal vasodilator ...
Most information currently available regarding vascular K+ channel function in diabetes concerns KATP channels. As for chronic hypertension, there are now several reports of impaired vascular relaxant responses to synthetic openers of KATP channels in long-term diabetes. These studies have mostly utilized the streptozotocin-injected rat model of diabetes and have examined vessels at 2.5 to 4 months after streptozotocin treatment. In this model in which plasma glucose levels are increased 3- to 4-fold, impaired relaxation of the isolated aorta122 123 124 and mesenteric vascular bed125 and reduced dilatation of large126 and small127 cerebral arteries in vivo typically develop. These changes are thought to be the result of a decreased number of vascular KATP channels and/or reduced sensitivity of these channels to synthetic openers. Nonspecific cytotoxic effects of streptozotocin seem an unlikely cause of these changes because, like other manifestations of vascular dysfunction, abnormal vasodilator ...
Potassium channel molecule. Computer model showing the structure of a bacterial potassium channel with four units arranged around an axis going through the first (and only visible) of four potassium ions (big purple sphere). From Bacillus cereus. - Stock Image C035/8257
A recent study (1) gives insight into how the lipids in the cell membranes affect how well one particular potassium channel functions. The particular channel the researchers investigated is one of the most studied potassium channels. This channel demonstrates how the function of other channels and pumps also may be affected by the composition of the cell membranes.. The researchers showed that the pore that lets potassium flow through the channel is fine-tuned by the physical characteristics of the lipid in the cell membrane. When the membrane allows protein in the pore of the channel to change more easily, potassium can get through faster.. This study changed two characteristics of the membrane that potassium channels sit in. The two characteristics of the membrane that the researchers changed were the temperature of the membrane, and the type of fats the membrane was made of. Both of these characteristics changed the fluidity of the membrane.. The researchers then determined whether the ...
An electrochemical gating model is presented to account for the effects described in the companion paper by M. R. Silver, M. S. Shapiro, and T. E. DeCoursey (1994. Journal of General Physiology, 103:519-548) of Rb+ and Rb+/K+ mixtures on the kinetics and voltage dependence of an inwardly rectifying (IR) K+ channel. The model proposes that both Rb+ and K+ act as allosteric modulators of an intrinsically voltage dependent isomerization between open and closed states. Occupancy of binding sites on the outside of the channel promotes channel opening and stabilizes the open state. Rb+ binds to separate sites within the pore and plugs IR channels. Occupancy of the pore by Rb+ can modify the rates of isomerization and the affinity of the allosteric sites for activator ions. The model also incorporates the proposed triple-barreled nature of the IR channel (Matsuda, H., 1988. Journal of Physiology. 397:237-258.) by proposing that plugging of the channel is a cooperative process involving a single site in ...
Global Markets Directs, Potassium Voltage Gated Channel Subfamily C Member 1 (Voltage Gated Potassium Channel Subunit Kv3.1 or Voltage Gated Potassium Channel Subunit Kv4 or KCNC1) - Pipeline
This enabled them to draw conclusions about its mechanism of action, which they describe in the current issue of Nature Communications. Neurons conduct information by way of electrical impulses through our body. Potassium channels are a key component of this electrical circuit and are controlled either by an electrical impulse or through signaling molecules. In man, the dysfunction of the so-called HCN potassium channels is associated with neurological disorders such as epilepsy and depression. Prof. Henning Stahlbergs team at the Biozentrum of the University of Basel has now elucidated the full structure of a bacterial counterpart of this type of potassium channel, which has provided new insights into its functioning.. ...
This e-book presents an overview of the different substances capable of modulating potassium channels in relation to various clinical indications in cardiology, pulmonology, endocrinology and neurology. The possible benefits and side effects of potassium channel modulators is discussed in correlation with biophysical and pharmacological properties of ion channels. Readers will learn how mutation of K+ channels can be conferred by molecular processes such as alternative splicing, RNA editing and posttranslational modifications. Altogether, this e-book will be of use to clinical practitioners, electrophysiologists and pharmacologists interested in the complicated but fascinating science of potassium channels.. ...
Energy dissipating systems (uncoupling proteins - UCPs, alternative oxidase - AOX, mitochondrial potassium channels) in physiological and pathological conditions: the activity of UCPs and AOXs in different eukaryotic organisms, UCP proteins in inflammation and circulatory diseases, mitochondrial potassium channels in cytoprotection, mitochondria and the endurance ...
July 29, 2013. Just 12 molecules of water cause the long post-activation recovery period required by potassium ion channels before they can function again. Using molecular simulations that modeled a potassium channel and its immediate cellular environment, atom for atom, University of Chicago scientists have revealed this new mechanism in the function of a nearly universal biological structure, with implications ranging from fundamental biology to the design of pharmaceuticals. Their findings were published online July 28 in Nature.. Our research clarifies the nature of this previously mysterious inactivation state. This gives us better understanding of fundamental biology and should improve the rational design of drugs, which often target the inactivated state of channels said Benoît Roux, PhD, professor of biochemistry and molecular biology at the University of Chicago.. Potassium channels, present in the cells of virtually all living organisms, are core components in bioelectricity ...
Effects of KRN4884 (5-amino-,i,N,/i,-[2-(2-chlorophenyl)ethyl]-,i,N,/i,-cyano-3-pyridinecarboxamidine), a novel K,sup,+,/sup, channel opener, on ionic currents were examined in rabbit femoral arterial myocytes (RFAMs). Under whole-cell clamp conditions where cells were superfused with 5.9 mM K,sup,+,/sup, bathing solution, KRN4884 elicited an outward current at −30 mV. KRN4884-induced current had a reversal potential of −78 mV and was abolished by application of glibenclamide (glib). KRN4884 was approximately 43 times more potent than levcromakalim in activating an ATP-sensitive K,sup,+,/sup, current (I,sub,K-ATP,/sub,). On the other hand, KRN4884 affected neither voltage-dependent Ca,sup,2+,/sup, nor delayed rectifier K,sup,+,/sup, channel currents. In the inside-out patch clamp configuration where cells were superfused with the symmetrical 140 mM K,sup,+,/sup, solution, KRN4884 activated 47 pS K,sup,+,/sup, channels in the presence of adenosine diphosphate. Similar 47 pS K,sup,+,/sup, ...
The following figure shows the location of the disease-causing mutations in hKv8.2 in CDSRE patients examined in this study. Three of these, W450G, G459D, and G461R, are located in the pore region of the hKv8.2 α-subunit. The missense mutations G459D and G461R affect the first and second glycine, respectively, of the Gly-Tyr-Gly motif, the characteristic potassium channel signature sequence. To understand the functional consequences of these mutations, the corresponding mutations (W467G, G476D, and G478R) were introduced into mKv8.2, and their effect on subunit localization in COS7L cells was examined. Like mKv8.2, the expression of either mKv8.2-W467G-EGFP, mKv8.2-G476D-EGFP, or mKv8.2-G478R-EGFP resulted in an intracellular localization [1753]. Voltage-gated K+ channels selectively transfer potassium ions through the plasma membrane in response to depolarization. The ion-conducting core of voltage-gated K+ channels is composed of four Kv-alpha subunits, which also possess the voltage sensor. ...
Fig. 2. KCNE1 inhibits KCNQ1 currents and depolarizes embryonic cells. (A) Tail currents were analyzed at −120 mV and normalized to the value followed after the 60-mV depolarizing pulse to estimate the voltage dependence of channel activation (n = 10 or 11). At voltages of 0 mV or less, addition of KCNE1 reduced the currents compared with KCNQ1 alone. (B) KCNQ1 (5 ng of mRNA) was expressed alone or together with 0.2 ng of KCNE1 mRNA. Each lane was loaded with equal amounts of protein (as estimated by Bradford test and Ponceau staining). Four consecutive biotinylation Western blots detected no clear alterations of KCNQ1 protein in the plasma membrane (densitometric analysis of all four gels normalized to the respective KCNQ1 band gave 1.0061 ± 0.1025 for KCNQ1 + KCNE1 injections). Analysis of membrane potential in vivo using DiSBAC voltage reporter dye reveals that KCNE1 mRNA expression depolarizes cells in the neurulating embryo. (C) Histograms showing normalized frequencies corresponding to ...
Potassium channels selectively conduct K(+) ions across cell membranes and have key roles in cell excitability. Their opening and closing can be spontaneous or controlled by membrane voltage or ligand binding. We used Ba(2+) as a probe to determine the location of the ligand-sensitive gate in an inwardly rectifying K(+) channel (Kir6.2). To a K(+) channel, Ba(2+) and K(+) are of similar sizes, but Ba(2+) blocks the pore by binding within the selectivity filter. We found that internal Ba(2+) could still access its binding site when the channel was shut, which indicates that the ligand-sensitive gate lies above the Ba(2+)-block site, and thus within or above the selectivity filter. This is in marked contrast to the voltage-dependent gate of K(V) channels, which is located at the intracellular mouth of the pore.
Sensory neurons, life-science tools related to Chemosensory Receptors (Olfactory, Vomeronasal, Trace Amine-Associated), Visual, Auditory, TRP channels and other GPCRs.
Gene Information Potassium channels are present in most mammalian cells where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein which has a greater tendency to allow potassium to flow into a cell rather than out of a cell is controlled by G-proteins. It associates with another G-protein-activated potassium channel to form a heteromultimeric pore-forming complex. [provided by RefSeq Jul 2008]. ...
This review has focused on the properties of the ATP-sensitive K-channel found in cardiac and skeletal muscle, and in pancreatic beta-cells. It is conceivable that this channel will be found in other cell types. In particular, it would be worthwhile looking for its presence in those cells in which electrical activity is linked to metabolism, glucose concentration, or oxygen levels. Obvious examples are the glucoreceptor neurons of mammalian brain and chemoreceptors such as those of the carotid body. While ATP-sensitive K-channels in cardiac and skeletal muscle membranes are rather similar, there are a few significant differences between these channels and that found in the beta-cell. Most notably, the latter is more sensitive to inhibition by ATP and sulphonylureas. It remains to be seen whether they also differ in the ability of nucleotides to activate the channel. Considerable confusion also still surrounds the physiological regulation of the ATP-sensitive K-channel in intact cells. Although the
This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The message for this gene is mainly expressed in the cortical distal tubules and collecting ducts of the kidney. The protein is highly sensitive to external pH and this, in combination with its expression pattern, suggests it may play an important role in renal potassium transport ...
Potassium channel (Protein Data Bank entry 1bl8) on a dark slate blue background with potassium ions shown in firebrick. The channel is comprised of four chains. Each chain has been rainbow-colored from blue at the N-terminus to red at the C-terminus, but only the surface of the channel is shown. The surface has been sliced with a per-model clipping plane. The surface cap color is plum except with opacity set to 0.8. The shininess and brightness have been set to 128 and 8, respectively, and the lights on the scene have been moved from their default positions. The subdivision quality (related to the smoothness of the spherical ions) is 5.0, and the molecular surface was computed with probe radius and vertex density set to 1.0 and 6.0, respectively. The entry Cavity and Tunnel Detection provides additional views of the same structure. ...
This is the Authors Original Manuscript of an article published by Taylor & Francis in Channels on 02 Jan 2018 available online: https://doi.org/10.1080/19336950.2017.1412151 ...
KCTD21 (potassium channel tetramerization domain containing 21), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
BioAssay record AID 2432 submitted by Johns Hopkins Ion Channel Center: Mode of action assay - molecular determinants for ztz240, a potentiator of KCNQ2 potassium channels.
Lipkind GM, Hanck DA, Fozzard HA. A structural motif for the voltage-gated potassium channel pore. Proc Natl Acad Sci U S A. 1995 Sep 26; 92(20):9215-9 ...
BioAssay record AID 2258 submitted by Johns Hopkins Ion Channel Center: Summary of probe development for potentiators of KCNQ2 potassium channels.
Kv1.2 Potassium Channel information including symptoms, causes, diseases, symptoms, treatments, and other medical and health issues.
High quality reagents for receptor, ion channel and enzyme research including potassium channel tools from Hello Bio - a trusted, affordable life science reagents supplier.
Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits.: Kir6.1\SUR2B has intrinsic sensitivity
心不全によるK_,ATP,チャネルの変調 : レシピエントから得た心筋による検討 Alterations in ATP-sensitive potassium channel sensitivity to ATP in failing human hearts ...
Experiments described in this report provide a strong argument for the existence of two distinct current components (I KF andI KS) in the slow sustained voltage-activated K+ current (I K) in the larval muscles ofDrosophila. Voltage-activated K+ current in the larval muscles ofDrosophila has been previously resolved into two distinct currents. With the data presented here, we can now resolve the total voltage-activated K+ current into three components. Resolution of I K intoI KS andI KF will be particularly helpful in analyzing the properties of these two currents, deciphering the functional role of each current in muscle excitability, and studying mechanisms underlying their function and regulation.. Channels carrying I KS are encoded by the Shab gene. I KS shares properties with the current generated by expressing Shabchannels in Xenopus oocytes. These properties include relative resistance to blockade by 4-AP and a relatively slow activation (Covarrubias et al., 1991; Tsunoda and Salkoff, ...
Our laboratory studies potassium channels which are key elements which control and shape electrical activity in the brain, heart, and other excitable tissues. These channels are major determinants of behavior and higher brain function. The potassium channels we study are involved in human disease (e.g. epilepsy, cardiac arrhythmia), basic physiology (e.g. control of blood pressure, protection from hypoxia), and higher brain function (e.g. learning and memory). Our approach is a comparative genom
This MATLAB function returns filtered state probabilities FS from conducting optimal conditional inference of the probabilities of the operative latent states in the regime-switching data Y.
Next-day shipping cDNA ORF clones derived from KCNE2 potassium voltage-gated channel subfamily E regulatory subunit 2 available at GenScript, starting from $99.00.
The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is
Int. J. Mol. Sci. 2002, 3 193 where M= M AM B=(M A+ M B) is the reduced mass of the nuclei Aand Bwith corresponding masses M A and M B, R is the vector connecting the nuclei, r denotes the set of the electronic coordinates measured from the centre of nuclear mass, and H el(r;R) is the so-called electronic Hamiltonian, which contains operators of the kinetic energy for the electrons and all ...
Katso sanan specific käännös englanti-suomi. Ilmainen Sanakirja on monipuolinen sanakirja netissä. Suomi, englanti, ruotsi ja monta muuta kieltä!
Outward tries to put a twist on the Western RPG formula, opting to focus on survival and strategy as opposed to action-focused combat. Is it successful? Read our Outward PS4 review to find out.
Euroopa Liidu L 215 Teataja Eestikeelne väljaanne Õigusaktid 61. aastakäik 23. august 2018 Sisukord III Muud aktid EUROOPA MAJANDUSPIIRKOND EMP ühiskomitee otsus nr 216/2016, millega muudetakse EMP lepingu
Tumor necrosis factor alpha modulates sodium-activated potassium channel SLICK in rat dorsal horn neurons via p38 MAPK activation pathway Kun Wang,1 Feng Wang,1 Jun-Ping Bao,2 Zhi-Yang Xie,1 Lu Chen,1 Bao-Yi Zhou,1 Xin-Hui Xie,2 Xiao-Tao Wu1,2 1Medical School of Southeast University, 2Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing, Peopleâ s Republic of China Abstract: The dorsal horn (DH) of the spinal cord is the integrative center that processes and transmits pain sensation. Abnormal changes in ion channel expression can enhance the excitability of pain-related DH neurons. Sodium-activated potassium (KNa) channels are highly expressed particularly in the central nervous system; however, information about whether rat DH neurons express the SLICK channel protein is lacking, and the direct effects on SLICK in response to inflammation and the potential signaling pathway mediating such effects are yet to be elucidated. Here, using cultured DH neurons, we have shown that
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium (By similarity).
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium. Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (By similarity).
Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ16 may be involved in the regulation of fluid and pH balance. In the kidney, together with KCNJ10, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules (PubMed:24561201 ...
Fluothane (halothane) is a small molecule pharmaceutical. Halothane was first approved as Fluothane on 1982-01-01. It is used to treat status asthmaticus in the USA. The pharmaceutical is active against potassium channel subfamily K member 9 and potassium channel subfamily K member 10. In addition, it is known to target potassium channel subfamily K member 2, potassium channel subfamily K member 12, potassium channel subfamily K member 3, potassium channel subfamily K member 5, potassium channel subfamily K member 13, potassium voltage-gated channel subfamily B member 1, G protein-activated inward rectifier potassium channel 2, and ferritin light chain.
Potassium channels, found throughout the animal and plant kingdoms, play important roles in maintaining membrane potentials and regulating action potential firing, shape, and duration, among other functions. Using the Xenopus laevis (frog) oocyte as model system, we induced high expression of sodium and potassium voltage-gated channels and recorded action potentials by a modification of the two-electrode voltage-clamp recording technique. The voltage-dependent sodium conductance was due to expression of the skeletal muscle NaV channel (NaV1.4) and the delayed rectifier voltage-dependent potassium conductance was due to expression of a Shaker (Kv1) potassium channel. Upon this background, we mixed different potassium-selective ion channels, such as inwardly rectifying potassium (KIR) channels, tandem pore domain (K2P) potassium channels and voltage-gated (KV) channels. We analyzed how these potassium channels affected firing thresholds, reliability of action potential generation, action potential
OBJECTIVE: To assess the influence of blocking smooth muscle large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels on the conducted dilation to ACh and isoproterenol. MATERIALS AND METHODS: Rat mesenteric arteries were isolated with a bifurcation, triple-cannulated, pressurized and imaged using confocal microscopy. Phenylephrine was added to the superfusate to generate tone, and agonists perfused into a sidebranch to evoke local dilation and subsequent conducted dilation into the feed artery. RESULTS: Both ACh- and isoproterenol-stimulated local and conducted dilation with similar magnitudes of decay with distance along the feed artery (2000μm: ∼15% maximum dilation). The gap junction uncoupler carbenoxolone prevented both conducted dilation and intercellular spread of dye through gap junctions. IbTx, TEA or 4-AP, blockers of large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels, did not affect conducted dilation to either agonist. A combination
TY - JOUR. T1 - Spontaneous contractions of the pig urinary bladder. T2 - The effect of ATP-sensitive potassium channels and the role of the mucosa. AU - Akino, Hironobu. AU - Chapple, Christopher R.. AU - McKay, Neil G.. AU - Cross, Rebecca L.. AU - Murakami, Shigetaka. AU - Yokoyama, Osamu. AU - Chess-Williams, Russell. AU - Sellers, Donna J.. PY - 2008/11. Y1 - 2008/11. N2 - OBJECTIVE: To investigate the influence of the mucosa on the inhibitory effects of the ATP-sensitive potassium channel (KATP channel) opener, cromakalim, on the spontaneous contractions of pig bladder strips from the bladder dome and trigone. Little is known about the influence of the mucosa on spontaneous contractions and whether the nature of these contractions differs between the bladder dome and trigone. MATERIALS AND METHODS: Paired longitudinal strips of female pig bladders were isolated from the dome and trigone. The mucosa was removed from one strip per pair and tissues were set up in organ baths. Spontaneous ...
The ATP-dependent potassium channels (KATP channels) were originally identified in isolated membrane patches prepared from guinea pig ventricular myocytes by Noma1 in 1983. Since their discovery in cardiac cells, KATP channels have also been discovered in many other tissues, such as smooth muscle, skeletal muscle, pancreas, and brain, in which they have been shown to couple cellular metabolism to membrane electrical activity.2 Primarily on the basis of studies using pharmacological tools, openers of KATP channels have been shown to elicit cardioprotective effects, whereas KATP channel antagonists have been shown to block the cardioprotective effects of KATP channel openers and the powerful protective effect produced by single or multiple brief episodes of ischemia to reduce myocardial infarct size, a phenomenon called ischemic preconditioning.3 Because the results of these previous studies were obtained indirectly by the use of pharmacological agonists and antagonists, the results of the present ...
TY - JOUR. T1 - Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons. T2 - Inhibition by BDS-I toxin. AU - Martina, Marco. AU - Metz, Alexia E.. AU - Bean, Bruce P.. PY - 2007/1/1. Y1 - 2007/1/1. N2 - We characterized the kinetics and pharmacological properties of voltage-activated potassium currents in rat cerebellar Purkinje neurons using recordings from nucleated patches, which allowed high resolution of activation and deactivation kinetics. Activation was exceptionally rapid, with 10-90% activation in about 400 μs at +30 mV, near the peak of the spike. Deactivation was also extremely rapid, with a decay time constant of about 300 μs near -80 mV. These rapid activation and deactivation kinetics are consistent with mediation by Kv3-family channels but are even faster than reported for Kv3-family channels in other neurons. The peptide toxin BDS-I had very little blocking effect on potassium currents elicited by 100-ms depolarizing steps, but the potassium ...
TY - JOUR. T1 - The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide. AU - McFalls, Edward O.. AU - Kelly, Rosemary F.. AU - Hu, Qingsong. AU - Mansoor, Abdul. AU - Lee, Joseph. AU - Kuskowski, Michael. AU - Sikora, Joseph. AU - Ward, Herbert B.. AU - Zhang, Jianyi. PY - 2007/11. Y1 - 2007/11. N2 - Within hibernating myocardium, it is uncertain whether a normal energetic state is present at baseline and whether maintaining that energy state during a catecholamine challenge is dependent on ATP-dependent potassium channel opening. In this study, 16 swine underwent a thoracotomy with placement of an external constrictor on the left anterior descending coronary artery (LAD) (hibernation model). Seven additional swine underwent a sham operation. At 10 wk, the myocardial energetic state in the LAD region was assessed by 31P-NMR spectroscopy, and the ratio of phosphocreatine to ATP (PCr/ATP) was ...
Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the KCND2 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential. Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the ...
Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013 ...
In a previous study we reported the presence of a large conductance K+ channel in the membrane of endoplasmic reticulum (ER) from rat hepatocytes. The channel open probability (Po) appeared voltage dependent and reached to a minimum 0.2 at +50 mV. Channel activity in this case was found to be totally inhibited at ATP concentration 2.5 mM, glibenclamide 100 μM and tolbutamide 400 μM. Existing evidence indicates an impairment of endoplasmic reticulum functions in ER stress condition. Because ER potassium channels have been involved in several ER functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the ER potassium channel function is altered in a high fat diet model of ER stress. Male Wistar rats were made ER stress for 2 weeks with a high fat diet. Ion channel incorporation of ER stress model into the bilayer lipid membrane allowed the characterization of K+ channel. Our results indicate that the channel Po was significantly ...
Fig. 1 Reduction of functional TRESK channels in DRG neurons and its association with pain in bone lesion-bearing rats.. (A and B) TRESK immunofluorescence staining in ipsilateral L4/5 DRG neurons from naïve, phosphate-buffered saline (PBS)-injected, or bone-localized MRMT-1 tumor-bearing rats. Representative images (A) and a summary for the mean fluorescence intensity of TRESK immunostaining (B) are shown. n = 224 to 230 cells (from six rats) per time point per group. Two-way analysis of variance (ANOVA) followed by Bonferroni post hoc test: F3,1818 = 116.2, ***P , 0.001. (C and D) TRESK protein (C) and mRNA (D) abundance in the cells described in (A). n = 6 to 7 rats per time point per group. Two-way ANOVA followed by either Bonferroni post hoc test, F3,40 = 4.21 (C), or one-way ANOVA followed by Tukey post hoc test, F2,16 = 20.54 (D), ***P , 0.001. N, naïve; P, PBS; M, MRMT-1. (E and F) Representative TRESK current traces and a summary for the current density of both the total background ...
TY - JOUR. T1 - Up-regulation of A-type potassium currents protects neurons against cerebral ischemia. AU - Deng, Ping. AU - Pang, Zhi Ping. AU - Lei, Zhigang. AU - Shikano, Sojin. AU - Xiong, Qiaojie. AU - Harvey, Brandon K.. AU - London, Barry. AU - Wang, Yun. AU - Li, Min. AU - Xu, Zao C.. PY - 2011/9/1. Y1 - 2011/9/1. N2 - Excitotoxicity is the major cause of many neurologic disorders including stroke. Potassium currents modulate neuronal excitability and therefore influence the pathological process. A-type potassium current (IA) is one of the major voltage-dependent potassium currents, yet its roles in excitotoxic cell death are not well understood. We report that, following ischemic insults, the IA increases significantly in large aspiny (LA) neurons but not medium spiny (MS) neurons in the striatum, which correlates with the higher resistance of LA neurons to ischemia. Activation of protein kinase Cα increases IA in LA neurons after ischemia. Cultured neurons from transgenic mice lacking ...
Cerebellar granule neurons (CGNs) are one of the most populous cells in the mammalian brain. They express an outwardly rectifying potassium current, termed a
Recent cloning of a family of genes encoding inwardly rectifying K+ channels has provided the opportunity to explain some venerable problems in membrane biology. An expanding number of novel inwardly rectifying K+ channel clones has revealed multiple channel subfamilies that have specialized roles i …
Read Kinetic Analysis of the Inhibitory Effect of Glibenclamide on KATP Channels of Mammalian Skeletal Muscle, The Journal of Membrane Biology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
The anti-contractile effect of perivascular adipose tissue (PVAT) is an important mechanism in the modulation of vascular tone in peripheral arteries. Recent evidence has implicated the XE991-sensitive voltage-gated Kv (KCNQ) channels in the regulation of arterial tone by PVAT. However, until now the in vivo pharmacology of the involved vascular Kv channels with regard to XE991 remains undetermined, since XE991 effects may involve Ca2+ activated BKCa channels and/or voltage-dependent Kv1.5 channels sensitive to diphenyl phosphine oxide-1 (DPO-1). In this study, we tested whether Kv1.5 channels are involved in the control of mesenteric arterial tone and its regulation by PVAT. Our study was also aimed at extending our current knowledge on the in situ vascular pharmacology of DPO-1 and XE991 regarding Kv1.5 and BKCa channels, in helping to identify the nature of K+ channels that could contribute to PVAT-mediated relaxation. XE991 at 30 µM reduced the anti-contractile response of PVAT, but had no effects
Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1.
Yılanı / dilatör yanıtları (basınç kasılmaların kâğıda çizilmesi kullanarak) ölçümleri ile paralel izole arteriyel miyositler (yama...
K11085 msbA; ATP-binding cassette, subfamily B, bacterial MsbA [EC:3.6.3.-] K11085 msbA; ATP-binding cassette, subfamily B, bacterial MsbA [EC:3.6.3.-] K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06160 pvdE; putative pyoverdin transport system ATP-binding/permease protein K15738 uup; ABC transport system ATP-binding/permease protein K21397 K21397; ABC transport system ATP-binding/permease protein K21397 K21397; ABC transport system ATP-binding/permease protein K23163 sbp; sulfate/thiosulfate transport system substrate-binding protein K02046 cysU; ...
Potassium Channels Inhibitors on signaling pathway are available at Adooq Bioscience. Check Potassium Channels pathway , inhibitors reviews and assay information.
In this recent study the researchers discovered a change in a potassium channel that is a major cause of secondary hypertension. Remember that normally an increase in aldosterone leads to an increase in sodium reabsorption in the kidney and a rise in blood pressure. Normally when there is an increase in potassium outside the cell, potassium will move into the cell.. In certain adrenal gland cells the resulting increase in membrane polarization (the difference in electrical charges across the membrane) leads to less aldosterone secretion. The lowering of aldosterone leads to less sodium reabsorption in the kidney, and thus lower blood pressure. In some people blood pressure is high and does not come down, because they have a gene that prevents this normal sequence.. In this particular study, a gene variant was found that affected part of a potassium channel. The change meant that the channel no longer allowed only potassium to pass. The channel allowed sodium to pass through the potassium channel ...
A compound of formula (I) wherein A, X, Y, Z, R.sub.1 and R.sub.24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I.sub.Kur-associated disorders, and other disorders mediated by ion channel function. ##STR00001##
History Early advancement of cardiac hypertrophy may be beneficial but suffered hypertrophic activation leads to myocardial dysfunction. the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity respectively. Results Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this JTP-74057 difference seen between JTP-74057 sham and shunt cardiomyocytes. Acute administration of ANG II (10?6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts but not in sham. Captopril treatment reversed SPP1 ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin transforming enzyme inhibition ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Conclusions Thus captopril treatment reveals a negative effect of ANG II on IK and IK1 which is usually PI3-K impartial whereas in the absence of angiotensin ...
Vernakalant Hcl(RSD-1235) is an investigational mixed ion channel blocker that can terminate acute atrial fibrillation (AF) in humans at 2 to 5 mg/kg and may be more atrial-selective than available agents; in treatment of antiarrhythmic ...
The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene. Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008 ...
Endogenous voltage-gated potassium currents were investigated in human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells using whole-cell voltage clamp recording. Depolarizing voltage steps from -70 mV triggered an outwardly rectified current in nontransfected HEK293 cells. This current had an amplitude of 296 pA at +40 mV and a current density of 19.2 pA/pF. The outward current was eliminated by replacing internal K+ with Cs+ and suppressed by the K+ channel blockers tetraethylammonium and 4-aminopyridine. Raising external K+ attenuated the outward current and shifted the reversal potential towards positive potentials as predicted by the Nernst equation. The current had a fast activation phase but inactivated slowly. These features implicate delayed rectifier (I(K))-like channels as mediators of the observed current, which was comparable in size to I(K) currents in many other cells. A small native inward rectifier current but no transient outward current I(A), the M current I(M), ...
Planar silicon chips with 1-2-μm etched holes (average resistance: 2.04 ± 0.02 MΩ in physiological buffer, n = 274) have been developed for patch-clamp recordings of whole-cell currents from cells in suspension. An automated 16-channel parallel screening system, QPatch 16, has been developed using this technology. A single-channel prototype of the QPatch system was used for validation of the patch-clamp chip technology. We present here data on the quality of patch-clamp recordings and from actual drug screening studies of human potassium channels expressed in cultured cell lines. Using Chinese hamster ovary (CHO) and human embryonic kidney cells (HEK), gigaseals of 4.1 ± 0.4 GΩ (n = 146) and high-quality whole-cell current recordings were obtained from hERG and KCNQ4 potassium channels. Success rates for gigaseal recordings varied from 40 to 95%, and 67% of the whole-cell configurations lasted for ,20 min. Cells were maintained in suspension up to 4 h in a cell storage facility that is ...
Planar silicon chips with 1-2-μm etched holes (average resistance: 2.04 ± 0.02 MΩ in physiological buffer, n = 274) have been developed for patch-clamp recordings of whole-cell currents from cells in suspension. An automated 16-channel parallel screening system, QPatch 16, has been developed using this technology. A single-channel prototype of the QPatch system was used for validation of the patch-clamp chip technology. We present here data on the quality of patch-clamp recordings and from actual drug screening studies of human potassium channels expressed in cultured cell lines. Using Chinese hamster ovary (CHO) and human embryonic kidney cells (HEK), gigaseals of 4.1 ± 0.4 GΩ (n = 146) and high-quality whole-cell current recordings were obtained from hERG and KCNQ4 potassium channels. Success rates for gigaseal recordings varied from 40 to 95%, and 67% of the whole-cell configurations lasted for ,20 min. Cells were maintained in suspension up to 4 h in a cell storage facility that is ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
The study which was led by Winthrop Professor David Hunt from UWAs Neuroecology Group and Lions Eye Institute, and included researchers from University College London, was published recently in the international Journal of Biological Chemistry.. Professor Hunt and his colleagues examined the genetic origins of a blinding disorder, in which symptoms include a loss of central vision and visual acuity, progressing on to a severe impairment of vision.. Earlier research found the disorder was caused by mutations in the gene that encodes a particular potassium channel protein, and Professor Hunt and his team looked at the effects of mutant channel proteins on the overall function of potassium channels.. Potassium channels are found throughout most living organisms and generate electrical signals. In the eye, the channels affect the function of cone and rod photoreceptors and the presence of mutant forms of channel proteins can be diagnosed quite specifically by a patients particular reaction to ...
The actions of the opioid agonist U50488H on I-A and I-K were examined in acutely isolated mouse hippocampal CA3 pyramidal neurons using the whole-cell patch clamp technique. U50488H caused a concentration dependent, rapidly developing and reversible inhibition of voltage-activated I-A and I-K. The inhibitory actions were still observed in the presence of 30 muM naloxone or 5 muM nor-binaltorphimine dihydrochloride. The IC50 values for the blockade of I-A and I-K were calculated as 20.1.9 and 3.7 muM, respectively. In the presence of 3.3 muM U50488H, repetitive stimulation induced use-dependent inhibition of I-A and I-K. A 10 muM concentration of U50488H positively shifted the half-activation membrane potential of I-A by +11 mV, but negatively shifted I-K by -14 mV. These results demonstrate that U50488H can directly inhibit neuronal I-A and I-K without involvement of the activation of kappa -opioid receptors. (C) 2001 Elsevier Science B.V. All rights ...
The Kvβ subunit of voltage-dependent potassium (Kv) channels has structural similarity to aldo-keto reductases (AKRs), enzymes that catalyze reduction of aldehyde groups to alcohols that are coupled to oxidation of an NADPH cofactor. However, it was unclear whether the Kvβ protein functioned in a catalytic capacity in its interaction with Kv channels, which allow voltage-sensitive conductance of potassium ions that is critical for action potentials in excitable cells. Weng et al. used spectrophotometric assays to show that purified rat Kvβ2 had associated NADPH and could reduce small-molecule aldehydes known to serve as substrates for other AKRs. Under other conditions, Kvβ2 could promote the reverse reaction--transfer of a hydride from an alcohol to reduce NADP+. Mutation of residues in the active site of the enzyme diminished the enzymatic activity. Application of a Kvβ substrate to Kv channels in inside-out patches from oocytes expressing the channel subunits decreased channel ...