The inhibition of voltage-gated potassium channels (Kv) plays a significant role in the cerebral hypoxia-induced cell death. of cerebral hypoxia. In conclusion AA/15-LOX/15-HETE induces vasoconstriction by down-regulating Kv channels and Kv2.1/1.5 channels are the targets. Our study also suggests a therapeutic strategy to improve ischemic vascular occlusion by lowering 15-HETE level and preventing Kv channel down-regulation which makes 15-LOX as a new target for the treatment of cerebral hypoxia. Keywords: 15-lipoxygenase (15-LOX) 15 acid (15-HETE) hypoxia Kv1.5 Kv2.1 Introduction Cerebral vascular disease is MP470 one of diseases with high morbidity and mortality 75 of which is caused by ischemic cerebrovascular. Hypoxia-induced vascular constriction was an important pathogenesis which could lead to cell death in cerebral ischemia [1 2 However the underlying mechanism is still unknown and the treatment could not accomplish the desired effect. In recent years hypoxia inhibits voltage-gated ...
The IUPHAR/BPS Guide to Pharmacology. Kv9.2 - Voltage-gated potassium channels. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
A surprising result of these studies is the augmentation of IL-4 production by Kv channel blockers in anergized CD4+ lymphocytes. This finding suggests that a more complex repertoire of functions may exist for Kv channels during other immunological responses of T cells. In anergized cells, IL-4 augmentation by Kv channel inhibitors may reflect the fact that low amplitude calcium signals bias the cytokine profile toward the transcription/production of IL-4 (and not IL-2) via the differential activation of NFATc and NFATp (44). Thus, diminished calcium signaling in partially primed (anergic) T cells may be analogous to diminished (APL-like) calcium signaling, which has been shown to induce IL-4 production upon restimulation of incompletely primed cells.. Another unexpected finding was that Kv channels do not regulate secondary physiological and immunological responses of effector cells. Thus, although Kv1.3 expression is increased, Kv channels neither contribute significantly to the membrane ...
The journal focuses on neuroimmunology and neuroinflammation, and the coverage extends to other basic and clinical studies related to neuroscience including molecular biology, psychology, pathology, physiology, endocrinology, pharmacology, oncology, etc.
Potassium voltage-gated channel subfamily C member 1 (KCNC1) antibody | P48547 | NGK2, Voltage-gated potassium channel subunit Kv3.1, Voltage-gated potassium channel subunit Kv4
Localization of voltage-gated potassium channels to specific subcellular compartments in neurons allows them to perform specific functions that modulate the overall electrophysiological properties of neurons. For instance, members of the Shaker family are localized to the axon of cortical pyramidal neurons where they contribute to the propagation of action potentials. Conversely, members of the Shal family of K+ channels are localized to the somatodendritic compartment of cortical pyramidal neurons where they inhibit initiation and propagation of action potentials. My research focuses on molecular mechanisms involved in targeting of these specific voltage-gated potassium channels to different subcellular compartments in neurons. By expressing chimeras between Kv1.4 and Kv4.2, two channels that are targeted to different neuronal compartments, the axon and the dendrites, respectively, as well as deletion mutants of Kv4.2 in cultured slices of rat cortical tissue we were able to identify a sixteen ...
Potassium voltage-gated channel subfamily E member 1 is a protein that in humans is encoded by the KCNE1 gene. Voltage-gated potassium channels (Kv) 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. KCNE1 is one of five members of the KCNE family of Kv channel ancillary or β subunits. It is also known as minK (minimal potassium channel subunit). KCNE1 is primarily known for modulating the cardiac and epithelial Kv channel α subunit, KCNQ1. KCNQ1 and KCNE1 form a complex in human ventricular cardiomyocytes that generates the slowly activating K+ current, IKs. Together with the rapidly activating K+ current (IKr), IKs is important for human ventricular repolarization. KCNQ1 is also essential for the normal function of many different ...
Voltage-dependent K+ (Kv) channels represent the most diverse group of K+ channels ubiquitously expressed in vascular smooth muscles. The Kv channels, together with other types of K+ conductances, such as Ca2+-activated (BKCa), ATP-sensitive (KATP), and inward rectifier, play an important role in the control of the cell membrane potential and regulation of the vascular contractility. Comparison of the expression of different Kv channel isoforms obtained from RT-PCR studies showed that virtually all Kv genes could be detected in vascular smooth muscle cells (VSMC). Based on the analysis of both mRNA and protein expressions, it is likely that Kv1.1, Kv1.2, Kv1.3, Kv1.5, Kv1.6, Kv2.1, and Kv3.1b channel isoforms are mainly responsible for the delayed rectifier current characterized electrophysiologically in most VSMC types studied to date. It has been recently demonstrated by our research group and by others that functional expression of multiple Kv channel α-subunits is not homogeneous and varies in
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 ...
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Molecular physiology of the voltage-gated potassium and sodium channels: ion channel diversity within the cardiovascular system ...
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Kv channels, the voltage-gated potassium channels, are encoded by KCN gene family. Kv channels are important in maintaining the resting membrane poten..
Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current (By similarity). Channel properties may be modulated by cAMP and subunit assembly.
Gene Information 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. This gene encodes a member of the potassium channel voltage-gated subfamily H. This member is a pore-forming (alpha) subunit of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms. [provided by RefSeq Jul 2008]. ...
COMMENT IA channel Reference: 1. Zhang, L. and McBain, J. Voltage-gated potassium currents in stratum oriens-alveus inhibitory neurons of the rat CA1 hippocampus, J. Physiol. 488.3:647-660, 1995. Activation V1/2 = -14 mV slope = 16.6 activation t = 5 ms Inactivation V1/2 = -71 mV slope = 7.3 inactivation t = 15 ms recovery from inactivation = 142 ms 2. Martina, M. et al. Functional and Molecular Differences between Voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus, J. Neurosci. 18(20):8111-8125, 1998. (only the gkAbar is from this paper) gkabar = 0.0175 mho/cm2 Activation V1/2 = -6.2 +/- 3.3 mV slope = 23.0 +/- 0.7 mV Inactivation V1/2 = -75.5 +/- 2.5 mV slope = 8.5 +/- 0.8 mV recovery from inactivation t = 165 +/- 49 ms 3. Warman, E.N. et al. Reconstruction of Hippocampal CA1 pyramidal cell electrophysiology by computer simulation, J. Neurophysiol. 71(6):2033-2045, 1994. gkabar = 0.01 mho/cm2 (number taken from the work by Numann et al. in guinea ...
Kv1.1, a Shaker-like voltage-gated potassium channel, is strongly expressed in a variety of neurons in adult rodents, where it appears to be involved in regulating neuronal excitability. Here we show that Kv1.1 is also ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
TY - JOUR. T1 - Functional blockade of the voltage-gated potassium channel Kv1.3 mediates reversion of T effector to central memory lymphocytes through SMAD3/p21 cip1 signaling. AU - Hu, Lina. AU - Gocke, Anne R.. AU - Knapp, Edward. AU - Rosenzweig, Jason M.. AU - Grishkan, Inna V.. AU - Baxi, Emily Grace. AU - Zhang, Hao. AU - Margolick, Joseph Bernard. AU - Whartenby, Katharine. AU - Calabresi, Peter. PY - 2012/1/6. Y1 - 2012/1/6. N2 - The maintenance of T cell memory is critical for the development of rapid recall responses to pathogens, but may also have the undesired side effect of clonal expansion of T effector memory (T EM) cells in chronic autoimmune diseases. The mechanisms by which lineage differentiation of T cells is controlled have been investigated, but are not completely understood. Our previous work demonstrated a role of the voltage-gated potassium channel Kv1.3 in effector T cell function in autoimmune disease. In the present study, we have identified a mechanism by which ...
BioAssay record AID 539300 submitted by ChEMBL: Inhibition of human voltage-gated potassium channel Kv1.3 expressed in L929 cells by whole-cell patch clamp assay.
Our results combined with previous studies (15, 16, 23, 29, 55) show that the functional and molecular diversification of Shaker and KCNQ families of voltage-gated K+ channels was largely complete before the divergence of cnidarians and bilaterians. Furthermore, Erg K+ channels, which constitute one of three bilaterian Ether-a-go-go gene subfamilies, are also highly conserved on functional level between cnidarians and vertebrates (70). The other two Ether-a-go-go subfamilies, Elk and Eag, have been identified in Nematostella (1). Thus, eight major classes of voltage-gated K+ channel are conserved between cnidarians and bilaterians, and the characteristic functional properties of six (Shaker, Shab, Shal, Shaw, KCNQ, and Erg) have now been shown to have evolved before the cnidarian/bilaterian divergence. Further support for an early diversification of voltage-gated K+ channels within parahoxozoans is the fact that Shaker, Shab, Shaw, and Erg channels can also be found in the placozoan Trichoplax ...
To gain insight into the mechanisms underlying their function, we have analyzed the currents recorded from channels formed only with KvLQT1 subunits and those coassembled from human minK and KvLQT1 subunits to form IKs channels. Noise-variance analyses showed the mixed channel complex to have a unitary conductance fourfold greater than that of homomeric KvLQT1 channels (Table I). As expected, IKs channels were found to activate and deactivate more slowly, to be less sensitive to voltage, and to select slightly more effectively against Cs+ and NH4+ ions than KvLQT1 channels (Tables I and II). When mutant IKs channels were formed with two minK subunits associated with LQTS and compared with wild-type IKs channels, they showed lower unitary conductances, a requirement for larger depolarizations to activate, and more rapid deactivation but no significant change in the relative permeability of monovalent cations (Tables I and II).. Our results generally agree with those of Yang and Sigworth (1998), ...
The human ether-á-go-go (eag)-related gene (hERG) voltage-gated potassium channel is the primary pore-forming subunit of the rapidly activating delayed-rectifier potassium current (IKr) in the heart (Warmke and Ganetzky, 1994; Sanguinetti et al., 1995; Trudeau et al., 1995). The physiological role of cardiac IKr is to repolarize myocytes during the terminal phase of cardiac action potentials (Sanguinetti and Jurkiewicz, 1990, 1991). Loss of function in hERG, either caused by inheritable mutations or pharmacological block, causes long QT syndrome, which can develop into ventricular arrhythmias and sudden cardiac death (Curran et al., 1995; Sanguinetti et al., 1995).. hERG is a member of the KCNH family of voltage-activated potassium (K+) channels, which are closely related to CNG and hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels (Guy et al., 1991; Warmke and Ganetzky, 1994). Like other voltage-gated potassium channels, KCNH channels are tetrameric, and each subunit has ...
Antibodies for proteins involved in positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization pathways, according to their Panther/Gene Ontology Classification
Distinguishing treatable causes for rapidly progressive dementia from those that are incurable is vital. Creutzfeldt-Jakob disease (CJD) and voltage-gated potassium channel complex-associated autoimmune encephalitis (VGKC AE) are 2 such conditions with disparate outcomes and response to treatment. To determine the differences in electroencephalography between CJD and VGKC AE, we performed a retrospective review of medical records and examined clinical data, neuroimaging, and electroencephalographs performed in patients admitted for evaluation for rapidly progressive dementia diagnosed with CJD and VGKC AE at the Johns Hopkins Hospital and Bayview Medical Center between January 1, 2007 and December 31, 2015. More patients in the VGKC AE group had seizures (12/17) than those with CJD (3/14; P = .008). Serum sodium levels were lower in those with VGKC AE ( P = .001). Cerebrospinal fluid (CSF) white blood cell count was higher in VGKC AE ( P = .008). CSF protein 14-3-3 ( P = .018) was more commonly ...
Voltage-gated ion channels play fundamental roles in excitable cells, such as neurons, where they enable electric signaling. Normally, this signaling is well controlled, but brain damage, alterations in the ionic composition of the extracellular solution, or dysfunctional ion channels can increase the electrical excitability thereby causing epilepsy. Voltage-gated ion channels are obvious targets for antiepileptic drugs, and, as a rule of thumb, excitability is dampened either by closing voltagegated sodium channels (Nav channels) or by opening voltage-gated potassium channels (Kv channels). For example, several classical antiepileptic drugs block the ion-conducting pore of Nav channels. Despite the large number of existing antiepileptic drugs, one third of the patients with epilepsy suffer from intractable or pharmacoresistant seizures.. Our research group has earlier described how different polyunsaturated fatty acids (PUFAs) open a Kv channel by binding close to the voltage sensor and, from ...
TY - JOUR. T1 - Voltage-gated K+ channels in rat small cerebral arteries. T2 - Molecular identity of the functional channels. AU - Albarwani, Sulayma. AU - Nemetz, Leah T.. AU - Madden, Jane A.. AU - Tobin, Ann A.. AU - England, Sarah K.. AU - Pratt, Phillip F.. AU - Rusch, Nancy J.. PY - 2003/9/15. Y1 - 2003/9/15. N2 - Voltage-gated potassium (Kv) channels represent an important dilator influence in the cerebral circulation, but the composition of these tetrameric ion channels remains unclear. The goals of the present study were to evaluate the contribution of Kv1 family channels to the resting membrane potential and diameter of small rat cerebral arteries, and to identify the α-subunit composition of these channels using patch-clamp, molecular and immunological techniques. Initial studies indicated that 1 μmol l-1 correolide (COR), a specific antagonist of Kv1 channels, depolarized vascular smooth muscle cells (VSMCs) in pressurized (60 mmHg cerebral arteries from -55 ± 1 mV to -34 ± 1 mV, ...
The potassium channel KCNQ4, expressed in the mammalian cochlea, has been associated tentatively with an outer hair cell (OHC) potassium current, IK,n, a current distinguished by an activation curve s
A transformed line of human embryonic kidney epithelial cells (HEK 293) is commonly used as an expression system for exogenous ion channel genes. Previously, it has been shown that these cells contain mRNAs for a variety of ion channels. Expression of some of these genes has been confirmed at the protein level. Patch-clamp electrophysiology experiments confirm the presence of multiple ion channels and molecular data agree with pharmacological profiles of identified channels. In this work, we show that endogenous voltage-gated potassium channels in HEK cells are a significant source of outward current at positive potentials. We show that both non-transfected HEK cells and HEK cells transfected with hyperpolarization-activated cyclic-nucleotide gated (HCN) channels have a significant amount of voltage-gated potassium (K(V)) current when certain tail current voltage-clamp protocols are used to assay HCN current activation. Specifically, tail current protocols that use a depolarized holding ...
This is a list of all employees at the Department of Biomedical Sciences. The list is sorted in alphabetical order in accordance to the employees first name.
Several CNS disorders associated with specific antibodies to ion channels, receptors, and other synaptic proteins have been recognised over the past 10 years, and can be often successfully treated with immunotherapies. Antibodies to components of voltage-gated potassium channel complexes (VGKCs), NMDA receptors (NMDARs), AMPA receptors (AMPARs), GABA type B receptors (GABA(B)Rs), and glycine receptors (GlyRs) can be identified in patients and are associated with various clinical presentations, such as limbic encephalitis and complex and diffuse encephalopathies. These diseases can be associated with tumours, but they are more often non-paraneoplastic, and antibody assays can help with diagnosis. The new specialty of immunotherapy-responsive CNS disorders is likely to expand further as more antibody targets are discovered. Recent findings raise many questions about the classification of these diseases, the relation between antibodies and specific clinical phenotypes, the relative pathological roles of
RecName: Full=Potassium voltage-gated channel subfamily C member 2 {ECO:0000312,MGI:MGI:96668};AltName: Full=Shaw-like potassium channel {ECO:0000250,UniProtKB:P22462};AltName: Full=Voltage-gated potassium channel Kv3.2 {ECO:0000303,PubMed:12000114 ...
Rationale: Autoantibodies to neuronal proteins contribute to the pathological process in an increasing number of childhood and adult epileptic syndromes and in encephalitic seizure-related disorders. Recently, antibodies to leucine-rich glioma inactivated 1 (LGI1), a protein within the voltage-gated potassium channel complex (VGKC), were identified in patients with faciobrachial dystonic seizures (FBDS). This represents the first clinically-distinctive immunotherapy-responsive adult-onset epilepsy syndrome. In this study we examined the prevalence of these and other antibodies to neuronal proteins in cohorts of patients with recent and with long standing epilepsies. Methods: Serum samples were collected from newly-diagnosed epilepsy patients, taken before the start of a clinical treatment trial (n=181) and from a cohort of consecutive epilepsy patients attending specialist clinics (n=235). All were tested for antibodies to the NMDA receptor, VGKC-complex, GAD and the glycine receptor using cell-based
BACKGROUND AND PURPOSE: Autoimmune voltage-gated potassium channel complex encephalitis is a common form of autoimmune encephalitis. Patients with seizures due to this form of encephalitis commonly have medically intractable epilepsy and may require immunotherapy to control seizures. It is important that radiologists recognize imaging characteristics of this type of autoimmune encephalitis and suggest it in the differential diagnosis because this seizure etiology is likely under-recognized. Our purpose was to characterize MR imaging findings in this patient population. ...
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. ...
responsiveness of arterial smooth muscle Kv7 channel subunits to intracellular cAMP/PKA signal activation follows the order of Kv7.5 || Kv7.4/Kv7.5 | Kv7.4.
Voltage-gated K+ (Kv) channels play a key role in establishing the resting membrane potential, shaping action potential repolarization and regulating spike frequency in many cell types. These channels often target specific plasma membrane regions where they probably assemble into signaling complexes. However, in most cases little is known about the mechanisms responsible for this localization, even though the modulation of voltage-gated ion channel surface expression and localization probably represents a central mechanism in the regulation of cellular excitability. Given the central role that the Kv2.1 delayed rectifier plays in neurons (Du et al., 2000; Misonou et al., 2005b), the heart (Nerbonne, 2000), pancreatic β cells (Tamarina et al., 2005) and vascular smooth muscle (Coppock et al., 2001), a greater understanding of the mechanisms regulating its surface localization is essential.. As originally noted by Trimmer and colleagues (Scannevin et al., 1996), Kv2.1 is expressed primarily in ...
As cancer cells have a hyperpolarized mitochondrial membrane and deficiency in Kv channel expression, it was postulated that the reversal of this observation may increase apoptosis and inhibit tumor growth. Bonnet and colleagues reported that the administration of DCA led to the switch from glycolysis to oxidative phosphorylation in the Krebs Cycle through inhibition of PDHK. This was associated with an increase in the production of reactive oxygen species and a decrease in hyperpolarization of the inner mitochondrial membrane, leading to efflux of proapoptotic proteins and apoptosis as measured by increased in TUNEL-positive cells. In addition, DCA also decreased the expression of survivin, an anti-apoptotic protein. DCA upregulated the expression of Kv channels in cancer cells, leading to efflux of potassium ions and further increased the proapoptotic effect of DCA. Such change in energy metabolism and apoptosis was not observed in normal cells. DCA was also shown to inhibit tumor growth both ...
During 2016, they have successfully established a working lab at the LEI and started working in new and ongoing projects. They were both involved in the application and award of a NHMRC equipment grant for an electroretinogram (ERG) equipment especially designed for use in laboratory rodent models.. This new equipment will assist LEI researchers in measuring visual function in animal models of visual disorders, important in the assessment and validation of novel treatment strategies and in the determination of disease progression. Dr Carvalho was directly responsible for the setup, installation and training of the new ERG which will be heavily used in her research projects.. The group currently holds six mouse lines that comprise four models of achromatopsia, an inherited retinal disorder that causes complete loss of colour vision, and two lines with targeted knock-out of voltage-gated potassium channel genes. For five of these lines, they are the sole holders in the world.. Also during 2016, Dr ...
Electrical signaling in living cells controls a wide variety of arguably important physiological processes such as feeling, thinking, and heartbeat. Electrophysiological signals are created by proteins known as ion channels, and modulating the behavior of ion channels will alter the processes they control. The goal of my research program is to develop modulators selective for ion channel subtypes, to more precisely alter electrophysiological signals and identify channel subunits that generate native currents. Establishing the molecular identity of voltage-gated potassium (Kv) channels has been a particularly challenging problem: mammalian channels arise from a family of more than 40 genes, and pore-forming subunits can assemble as heterotetramers. Despite substantial and enduring efforts, few modulators of Kv channel activity have been discovered that are highly selective between channel subtypes. This is perhaps due to a high degree of sequence conservation between subfamily members in ...
Comments: The persistent component of the K current. Reference: Voltage-gated K+ channels in layer 5 neocortical pyramidal neurones from young rats:subtypes and gradients,Korngreen and Sakmann, J. Physiology, 2000. Shifted -10 mv to correct for junction potential. Corrected rates using q10 = 2.3, target temperature 34, orginal 21 ...
Yi, Fan Teah and Abduraman, Muhammad Asyraf and Amanah, Azimah and Adenan, Mohd Ilham and Sulaiman, Shaida Fariza and Mei, Lan Tan (2017) Data on the construction of a recombinant HEK293 cell line overexpressing hERG potassium channel and examining the presence of hERG mRNA and protein expression. Data in Brief, 14. pp. 584-591. ISSN 2352-3409 ...
Complete information for KCNE4 gene (Protein Coding), Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 4, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
KCNE2 / MiRP1 antibody (potassium voltage-gated channel, Isk-related family, member 2) for ICC/IF, IHC-Fr, IP, WB. Anti-KCNE2 / MiRP1 pAb (GTX54783) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
pep:known chromosome:VEGA66:2:181075579:181135214:-1 gene:OTTMUSG00000016558 transcript:OTTMUST00000040028 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Kcnq2 description:potassium voltage-gated channel, subfamily Q, member 2 ...
The human ether-a-go-go-related gene (hERG) encodes channels mediating the rapid delayed rectifier K+ current (IKr). IKr participates in cardiac action potential (AP) repolarisation and may also protect the ventricles against premature stimulation. The heart is exposed to acidosis (low pH) in a number of pathological conditions including myocardial ischemia. Extracellular acidosis is known to modulate hERG current (IhERG) function, although a number of aspects of the modulation remain incompletely understood. The aims of this investigation were to establish the effects of acidosis on: (i) IhERG amplitude, kinetics and the response to premature stimulation at mammalian physiological temperature; (ii) the hERG blocking potency of selected anti arrhythmic drugs. Whole-cell patch-clamp recordings of IhERG were made from mammalian cells (CHO or HEK 293) at 37 QC. Lowering external pH from 7.4 to 6.3 reduced the magnitude of IhERG by reducing macroscopic hERG conductance and modulating IhERG kinetics, ...
VCF (voltage clamp fluorimetry) provides a powerful technique to observe real-time conformational changes that are associated with ion channel gating. The present review highlights the insights such experiments have provided in understanding Kv (voltage-gated potassium) channel gating, with particular emphasis on the study of mammalian Kv1 channels. Further applications of VCF that would contribute to our understanding of the modulation of Kv channels in health and disease are also discussed.. ...
Tinnitus is an unpleasant sensation often described as ringing in the ears that may manifest in a variety of settings, e.g. after acoustic trauma, as a side effect of medication, or spontaeously [1]. Epidemiological studies suggest that close to 15% of the adult population may be affected to varying degrees [2]. In severe cases, patients develop a chronic course of illness marked by sleep disturbances, depressed mood, increased muscle tension and loss of attention, or other comorbidities [3]. While the underlying biological mechanisms are still incompletely understood, early research into the pharmacological treatment of tinnitus has emphasized a role for cellular ion regulation and transport [4]. Interest in the disruption of ion conductance in the inner ear has been renewed following recent discoveries in other heritable pathologies of auditory perception. Specifically, dysfunctional K+-extruding cells of the stria vascularis are known to interfere with potassium homeostasis and the ...
The human ether-a-go-go related gene (hERG) potassium channel plays a major role in the repolarization of the cardiac action potential. Inhibition of the hERG function by mutations or a wide variety of pharmaceutical compounds cause long QT syndrome and lead to potentially lethal arrhythmias. For detailed insights into the structural and biochemical background of hERG function and drug binding, the purification of recombinant protein is essential. Because the hERG channel is a challenging protein to purify, fast and easy techniques to evaluate different expression, solubilization and purification conditions are of primary importance. Here, we describe the generation of a set of 12 monoclonal antibodies against hERG. Beside their suitability in western blot, immunoprecipitation and immunostaining, these antibodies were used to establish a sandwich ELISA for the detection and relative quantification of hERG in different expression systems. Furthermore, a Fab fragment was used in fluorescence size ...
Potassium voltage-gated channel, Shab-related subfamily, member 1, also known as KCNB1 or Kv2.1, is a protein that, in humans, is encoded by the KCNB1 gene. Potassium voltage-gated channel subfamily B member one, or simply known as KCNB1, is a delayed rectifier and voltage-gated potassium channel found throughout the body. The channel has a diverse number of functions. However, its main function, as a delayed rectifier, is to propagate current in its respective location. It is commonly expressed in the central nervous system, but may also be found in pulmonary arteries, auditory outer hair cells, stem cells, the retina, and organs such as the heart and pancreas. Modulation of K+ channel activity and expression has been found to be at the crux of many profound pathophysiological disorders in several cell types. Potassium channels are among the most diverse of all ion channels in eukaryotes. With over 100 genes coding numerous functions, many isoforms of potassium channels are present in the body, ...