- subunits
- Ion channels are made up of subunits, which combine to form structures with a central aqueous pore. (bmj.com)
- Based on sequence homology of the hydrophobic transmembrane cores, the alpha subunits of voltage-gated potassium channels are grouped into 12 classes. (wikipedia.org)
- These subunits do not conduct current on their own but rather modulate the activity of Kv channels. (wikipedia.org)
- Typically, vertebrate voltage-gated K+ channels are tetramers of four identical subunits arranged as a ring, each contributing to the wall of the trans-membrane K+ pore. (wikipedia.org)
- Channel mutation studies have revealed the parts of the subunits that are essential for ion selectivity. (wikipedia.org)
- As K+ passes through the pore, interactions between potassium ions and water molecules are prevented and the K+ interacts with specific atomic components of the Thr-Val-Gly-[YF]-Gly sequences from the four channel subunits . (wikipedia.org)
- Wang et al (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. (tocris.com)
- Voltage-gated Na + channels in the brain are complexes of a 260 kDa α subunit in association with auxiliary β subunits (β1-β4) of 33-36 kDa (Catterall, 2000). (jneurosci.org)
- 50% in the transmembrane domains of human sodium channel α subunits and those of the simplest multicellular eukaryotes. (jneurosci.org)
- The mammalian genome contains nine functional voltage-gated sodium channel α subunits, which differ in patterns of tissue expression and biophysical properties. (jneurosci.org)
- This protein belongs to the potassium channel KCNE family and is one five single transmembrane domain voltage-gated potassium (Kv) channel ancillary subunits. (wikipedia.org)
- The number of functionally distinct channels in native tissues is further increased by heteromultimeric assembly of potassium channel α-subunits with other α- and β-subunits and other modifications such as alternative splicing of mRNAs, glycosylation, and phosphorylation. (aspetjournals.org)
- transmembrane
- As the transmembrane voltage changes a voltage gated sodium channel opens and ions pass rapidly down an electrochemical gradient from a high concentration outside the cell through the channel pore into the cell. (bmj.com)
- The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. (wikipedia.org)
- They are described as minimally having two transmembrane helices flanking a loop which determines the ion selectivity of the channel pore. (wikipedia.org)
- Many eukaryotic channels have four additional transmembrane helices (TM) (Pfam PF00520), related to or vestigial of voltage gating. (wikipedia.org)
- Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. (wikipedia.org)
- Several charged residues of the VSD, in particular four arginine residues located regularly at every third position on the S4 segment, are known to move across the transmembrane field and contribute to the gating charge. (wikipedia.org)
- The α subunit contains the voltage sensors and the ion-conducting pore in four internally repeated domains (I-IV), which each consists of six α-helical transmembrane segments (S1-S6) and a pore loop connecting S5 and S6 (Catterall, 2000). (jneurosci.org)
- neuronal
- Zhang et al (2011) AKAP79/150 signal complexes in G-protein modulation of neuronal ion channels. (tocris.com)
- Geier et al (2011) Dynamic interplay of excitatory and inhibitory coupling modes of neuronal L-type calcium channels. (tocris.com)
- 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. (bertin-bioreagent.com)
- KCNQ (K v 7) channels underlie a voltage-gated K + current best known for control of neuronal excitability, and its inhibition by G q/11 -coupled, muscarinic signaling. (frontiersin.org)
- We studied here the coupling of different molecularly defined P2Y receptors to neuronal G protein-gated inward rectifier K + (GIRK) channels. (aspetjournals.org)
- Title: Polarized axonal surface expression of neuronal KCNQ potassium channels is regulated by calmodulin interaction with KCNQ2 subunit. (nih.gov)
- KCNQ
- Potent and selective blocker of K V 7 (KCNQ) voltage-gated potassium channels. (tocris.com)
- Wang et al (2000) Molecular basis for differential sensitivity of KCNQ and I Ks channels to the cognitive enhancer XE991. (tocris.com)
- Recent evidence has implicated the XE991-sensitive voltage-gated K V (KCNQ) channels in the regulation of arterial tone by PVAT. (frontiersin.org)
- These channels are present in VSMCs and very potently inhibited by the KCNQ channel blocker XE991. (frontiersin.org)
- Studies have indicated expression of KCNQ channels in airway smooth muscle (ASM), a tissue that is predominantly regulated by muscarinic receptor signaling. (frontiersin.org)
- Therefore, we investigated the function of KCNQ channels in rodent ASM and their interplay with G q/11 -coupled M 3 muscarinic receptors. (frontiersin.org)
- KCNQ channels begin to activate at voltages near resting potentials for ASM cells, and indeed XE991 depolarized resting membrane potentials. (frontiersin.org)
- Thus, we were surprised to see that KCNQ had no affect on membrane voltage or muscle contractility following muscarinic activation. (frontiersin.org)
- However, a role for KCNQ channels was revealed when BK-K + channel activities are reduced. (frontiersin.org)
- While KCNQ channels do control resting potentials, they appear to play a redundant role with BK calcium-activated K + channels during ASM muscarinic signaling. (frontiersin.org)
- These findings indicate that KCNQ channels can be recruited via agonists to oppose muscarinic evoked contractions and may be of therapeutic value as bronchodilators. (frontiersin.org)
- Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term "noxacusis" to distinguish from hyperacusis without pain) that can accompany hearing loss. (pnas.org)
- Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage. (pnas.org)
- mutations
- In an effort to understand the functional consequences of particular channel mutations, cDNA techniques have been utilised to express mutant and normal channels in in vitro biological systems, allowing currents to be measured across either groups of channels in membrane patches or single channels. (bmj.com)
- Genetic approaches include screening for behavioral changes in animals with mutations in K+ channel genes. (wikipedia.org)
- Studies of genetic forms of epilepsy, chronic pain, and migraine caused by mutations in ion channels have given crucial insights into molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological disorders. (jneurosci.org)
- Gain-of-function missense mutations in the brain type-I sodium channel Na V 1.1 are a primary cause of generalized epilepsy with febrile seizures plus. (jneurosci.org)
- Loss-of-function mutations in Na V 1.1 channels cause severe myoclonic epilepsy of infancy, an intractable childhood epilepsy. (jneurosci.org)
- Mutations in the peripheral sodium channel Na V 1.7 cause familial pain syndromes. (jneurosci.org)
- Familial hemiplegic migraine is caused by mutations in the calcium channel, Ca V 2.1, which conducts P/Q-type calcium currents that initiate neurotransmitter release. (jneurosci.org)
- Because of the importance of their functions and the complexity of their structures, these two ion channels are targets for numerous mutations that cause diseases of hyperexcitability, including epilepsy, migraine, chronic pain, periodic paralysis, and cardiac arrhythmia. (jneurosci.org)
- Channels might lose or gain function as a result of mutations in the promotor or codings region of a gene. (aspetjournals.org)
- The inherited LQTS associated KCNQ1/KCNE1 and HERG/KCNE2 channel mutations cause a decrease in net repolarizing current I K by reducing potassium currents through "dominant-negative" or "loss-of-function" mechanisms, whereas the aLQTS is the result of I K -blockade. (aspetjournals.org)
- However, myotonia caused by CLCN1 mutations can occasionally be clinically indistinguishable from myotonia caused by sodium channel mutations ( SCN4A mutations) resulting in the similar disease paramyotonia congenita . (wikipedia.org)
- relatively little is known about ERG function in the brain, although mutations in ERG channels have recently been linked to schizophrenia. (jneurosci.org)
- KCNQ1
- Blocks K V 7.2+7.3 (KCNQ2+3) / M-currents (IC 50 = 0.6 - 0.98 μ M) and K V 7.1 (KCNQ1) homomeric channels (IC 50 = 0.75 μ M) but is less potent against K V 7.1/minK channels (IC 50 = 11.1 μ M). Augments hippocampal ACh release and is a cognitive enhancer following oral administration in vivo . (tocris.com)
- In addition, KCNE2 forms reciprocally regulating tripartite complexes in the choroid plexus epithelium with the KCNQ1 α subunit and the sodium-dependent myo-inositol transporter, SMIT1. (wikipedia.org)
- In these cells, KCNQ1-KCNE2 K+ channels, which are constitutively active, provide a conduit to return K+ ions back to the stomach lumen. (wikipedia.org)
- While KCNQ1 channels are inhibited by low extracellular pH, KCNQ1-KCNE2 channels activity is augmented by extracellular protons, an ideal characteristic for their role in parietal cells. (wikipedia.org)
- KCNE2 forms constitutively active K+ channels with KCNQ1 in the basolateral membrane of thyroid epithelial cells. (wikipedia.org)
- KCNQ1-KCNE2 is required for optimal iodide uptake into the thyroid by the basolateral sodium iodide symporter (NIS). (wikipedia.org)
- subunit
- Each subunit is composed of six membrane spanning hydrophobic α-helical sequences, as well as a voltage sensor in S1-S4. (wikipedia.org)
- 70%, knock-out of any of the three sodium channel α subunit genes expressed primarily in adult brain ( SCN1A , SCN2A , and SCN8A ) is lethal, demonstrating that each channel performs some nonredundant function. (jneurosci.org)
- MiRP1 is a voltage-gated potassium channel accessory subunit (beta subunit) associated with Long QT syndrome. (wikipedia.org)
- KCNE2 forms complexes there with the voltage-gated potassium channel α subunit, Kv1.3. (wikipedia.org)
- selective
- Channels are selective for particular ion species and can be gated, altering conformation to open or close. (bmj.com)
- Voltage-gated K+ channels are selective for K+ over other cations such as Na+. (wikipedia.org)
- Studies of a mouse model show that this disease is caused by selective loss of sodium current and excitability of GABAergic inhibitory interneurons, which leads to hyperexcitability, epilepsy, and ataxia. (jneurosci.org)
- Cation selective channels play important roles in physiological processes such as secretory transduction, control of ion homeostasis, cell volume, vesicle cycling, and electrical control of excitable tissues. (aspetjournals.org)
- Potassium-selective channels are the most genetically diverse of all cation channels. (aspetjournals.org)
- Starting with the first cloned potassium selective ion channel from Drosophila melanogaster , Shaker, more than 100 potassium channels have been identified. (aspetjournals.org)
- action potentials
- The voltage-gated K+ channels that provide the outward currents of action potentials have similarities to bacterial K+ channels. (wikipedia.org)
- proteins
- Interestingly, the HVCN1 and Putative tyrosine-protein phosphatase proteins do not contain an expected ion conduction pore domain, but rather have homology only to the voltage sensor domain of voltage gated ion channels. (wikipedia.org)
- Study of the altered properties of voltage-gated K+ channel proteins produced by mutated genes has helped reveal the functional roles of K+ channel protein domains and even individual amino acids within their structures. (wikipedia.org)
- We show that rat vestibular calyces express an unusual mix of voltage-gated Na and K channels and scaffolding, cell adhesion, and extracellular matrix proteins, which may hold the ion channels in place. (pubmedcentralcanada.ca)
- Ion channels are integral membrane proteins that help establish and control the small voltage gradient across the plasma membrane of living cells by allowing the flow of ions down their electrochemical gradient. (bertin-bioreagent.com)
- Cation channels are membrane proteins that provide controlled pathways for ion passage through cellular membranes. (aspetjournals.org)
- The importance of cation channels is also amplified by the fact that many therapeutic drugs mediate their effects by targeting these proteins. (aspetjournals.org)
- KCNQ3
- Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2/KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon. (nih.gov)
- inward-rectifier
- This also includes the 2-TM Inward-rectifier potassium channels (Pfam PF01007) found primarily in eukaryotes. (wikipedia.org)
- The other gated classifications include activation and inactivation by second messengers, inward-rectifier potassium channels, calcium-activated potassium channels, two-pore-domain potassium channels, light-gated channels, mechano-sensitive ion channels, and cyclic nucleotide-gated channels. (bertin-bioreagent.com)
- Other G i/o -linked receptors that inhibit N-type Ca 2+ channels usually also activate G protein-gated inward rectifier (GIRK or Kir3) channels. (aspetjournals.org)
- XE991
- However, until now the in vivo pharmacology of the involved vascular K V channels with regard to XE991 remains undetermined, since XE991 effects may involve Ca 2+ activated BK Ca channels and/or voltage-dependent K V 1.5 channels sensitive to diphenyl phosphine oxide-1 (DPO-1). (frontiersin.org)
- Our study was also aimed at extending our current knowledge on the in situ vascular pharmacology of DPO-1 and XE991 regarding K V 1.5 and BK Ca channels, in helping to identify the nature of K + channels that could contribute to PVAT-mediated relaxation. (frontiersin.org)
- BK Ca channels and/or DPO-1 sensitive K V 1.5 channels in VSMCs are not the downstream mediators of the XE991 effects on PVAT-dependent arterial vasorelaxation. (frontiersin.org)
- currents
- Calcium accumulation during triggering stimuli appears to attenuate ERG currents, leading to membrane potential depolarization and increased input resistance, two critical elements generating persistent firing. (jneurosci.org)
- Our results suggest that a reduction in the currents normally mediated by Ether-a-go-go-Related Gene (ERG) K + channels contributes to persistent firing in neocortical pyramidal cells. (jneurosci.org)
- ions
- The normally negatively charged cell interior depolarises, causing voltage gated potassium channels to open and potassium ions to leave the cell, restoring the resting membrane potential. (bmj.com)
- It may seem counterintuitive that a channel should allow potassium ions but not the smaller sodium ions through. (wikipedia.org)
- Whereas some ion channels permit the passage of ions based on charge, others conduct based on a ionic species, such as sodium or potassium. (bertin-bioreagent.com)
- blockers
- Three chemically diverse ERG channel blockers (terfenadine, ErgToxin-1, and E-4031) abolished persistent firing and the underlying increase in input resistance in deep pyramidal cells in temporal and prefrontal association neocortex. (jneurosci.org)
- membrane
- This process is remarkably reproducible despite the confounding fact that, at the membrane potential reached during the AP plateau, the driving force for Ca 2+ entry through a single Ca v 1.2 channel is not sufficient to reliably activate RyRs. (washington.edu)
- The high resolution crystallographic structure of the rat Kvα1.2/β2 channel has recently been solved (Protein Databank Accession Number 2A79), and then refined in a lipid membrane-like environment (PDB: 2r9r). (wikipedia.org)
- The structure of the mammalian voltage-gated K+ channel has been used to explain its ability to respond to the voltage across the membrane. (wikipedia.org)
- Upon opening of the channel, conformational changes in the voltage-sensor domains (VSD) result in the transfer of 12-13 elementary charges across the membrane electric field. (wikipedia.org)
- The first are voltage-gated ion channels which open and close in response to membrane potential. (bertin-bioreagent.com)
- Opening of vascular smooth muscle cell (VSMC) K + channels causes K + efflux and membrane hyperpolarization, which leads to reduced Ca 2+ influx though L-type Ca V 1.2 channels and consequently arterial relaxation ( Nelson and Quayle, 1995 ). (frontiersin.org)
- The control of membrane voltage by K + channels serves as a negative feedback to oppose voltage-dependent calcium influx pathways that contribute to airway smooth muscle (ASM) contraction. (frontiersin.org)
- functional
- Kvα11.x - ether-a-go-go potassium channels: Kv11.1 (KCNH2) - hERG, Kv11.2 (KCNH6), Kv11.3 (KCNH7) Kvα12.x: Kv12.1 (KCNH8), Kv12.2 (KCNH3), Kv12.3 (KCNH4) Unable to form functional channels as homotetramers but instead heterotetramerize with Kvα2 family members to form conductive channels. (wikipedia.org)
- Likewise, functional impairment of channel function might result from regulatory derangements or by autoantibodies. (aspetjournals.org)
- regulate
- There are commonly additional regulatory domains which serve to regulate ion conduction and channel gating. (wikipedia.org)
- We have also discovered that Ca v 1.3 channels that regulate excitability in neurons often display the same cooperative behavior. (washington.edu)
- Because of this and its ability to regulate multiple different ion channels, KCNE2 exerts considerable influence on a number of cell types and tissues. (wikipedia.org)
- KCNE2 was originally discovered to regulate hERG channel function. (wikipedia.org)
- KCNE2 may also regulate hyperpolarization-activated, cyclic-nucleotide-gated (HCN) pacemaker channels in human heart and in the hearts of other species, as well as the Cav1.2 voltage-gated calcium channel. (wikipedia.org)
- pore
- Finally, the other classifications are based on less normal characteristics such as two-pore channels and transient receptor potential channels. (bertin-bioreagent.com)
- ligand
- The two principal classes are voltage and ligand gated channels. (bmj.com)
- A ligand gated ion channel opens following binding of a ligand to the receptor portion of the channel. (bmj.com)
- There are voltage-gated ion channels, ligand-gated, other gating systems, and finally those that are classified differently, having more exotic characteristics. (bertin-bioreagent.com)
- Ligand-gated ion channels are also known as ionotropic receptors and they open in response to specific ligand molecules binding to the extracellular domain of the receptor protein. (bertin-bioreagent.com)
- MiRP1
- Potassium voltage-gated channel subfamily E member 2 (KCNE2), also known as MinK-related peptide 1 (MiRP1), is a protein that in humans is encoded by the KCNE2 gene on chromosome 21. (wikipedia.org)
- inactivation
- Reduced calmodulin expression accelerates transient outward potassium current inactivation in diabetic rat heart. (nih.gov)
- underlie
- The broad expression of ERG channels and the ability of ERG blocks to abolish persistent firing evoked by both synaptic and intracellular step stimuli suggest that modulation of ERG channels may underlie many forms of persistent activity observed in vivo . (jneurosci.org)
- intracellular calcium
- Polycystin 2 acts both as an intracellular calcium channel and a modulator to alter intracellular signaling pathways. (washington.edu)
- hERG
- New compounds such as the HERG channel activator (3 R ,4 R )-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluoro-phenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid (RPR260243) will enable us to increase our understanding in cation channel modulation and to test the concept of channel activation as a clinically relevant principle in treatment of channelopathies. (aspetjournals.org)
- influx
- In ventricular myocytes, excitation-contraction (EC) coupling occurs via a Ca 2+ induced Ca 2+ release mechanism such that the depolarization created by an action potential (AP) triggers Ca 2+ influx through voltage-dependent L-type Ca 2+ channels (i.e. (washington.edu)
- Using electrophysiological, and optical approaches, we have found that an allosteric interaction between the C-terminal domains of voltage-gated Ca V 1.2 channels induces an increase in the open probability of the channels that amplifies Ca 2+ influx during the AP and contributes to reproducible EC-coupling. (washington.edu)
- Suppression of Ca 2+ influx through voltage-activated Ca 2+ channels by 200 μM Cd 2+ resulted mainly in moderate increase of steady-state firing frequency and increase of single AP repolarization rate, however, without abolishing the basic pattern of tonic firing. (50webs.com)
- modulation
- Ooi et al (2013) Triple cysteine module within M-type K+ channels mediates reciprocal channel modulation by nitric oxide and reactive oxygen species. (tocris.com)
- aqueous
- However in an aqueous environment, potassium and sodium cations are solvated by water molecules. (wikipedia.org)
- selectivity
- They include the amino acid sequence (Thr-Val-Gly-Tyr-Gly) or (Thr-Val-Gly-Phe-Gly) typical to the selectivity filter of voltage-gated K+ channels. (wikipedia.org)
- When moving through the selectivity filter of the potassium channel, the water-K+ interactions are replaced by interactions between K+ and carbonyl groups of the channel protein. (wikipedia.org)
- The diameter of the selectivity filter is ideal for the potassium cation, but too big for the smaller sodium cation. (wikipedia.org)
- Hence, the passage of potassium cations through this selectivity filter is strongly favored over sodium cations. (wikipedia.org)
- protein
- Hence the potassium cations are well "solvated" by the protein carbonyl groups, but these same carbonyl groups are too far apart to adequately solvate the sodium cation. (wikipedia.org)
- The protein encoded by this gene forms a potassium channel tha. (bertin-bioreagent.com)
- Voltage-gated sodium and calcium channels are closely related members of the ion channel protein superfamily ( Yu and Catterall, 2004 ). (jneurosci.org)
- gene
- Abnormalities of ion channel function are responsible for a variety of non-neurological disorders including Bartter syndrome, X linked nephrolithiasis, neonatal hyperinsulinism, long QT syndromes, and most notably defects in function of the CFTR chloride channel gene causing cystic fibrosis. (bmj.com)
- Such genetic methods allowed the genetic identification of the "Shaker" K+ channel gene in Drosophila before ion channel gene sequences were well known. (wikipedia.org)
- We found multiple lines of evidence suggesting that a component of the underlying hyperexcitability associated with persistent firing reflects a reduction in the standing (leak) K + current mediated by Ether-a-go-go-Related Gene (ERG) channels. (jneurosci.org)
- transient
- This charge transfer is measured as a transient capacitive current that precedes opening of the channel. (wikipedia.org)
- cation channel
- Shortage in cation channel activators prevents testing of efficiency of activators in a variety of indications. (aspetjournals.org)
- This shortage might result from the relative incapability of modern drug screening methods, but increasing knowledge about cation channel activator binding and action might enable us in the future to use in silico-guided drug design of channel modulators. (aspetjournals.org)
- channelopathies
- One might therefore expect that diseases of ion channels or channelopathies would not be compatible with life. (bmj.com)
- In a variety of channelopathies, ion channel function is reduced, and activators of cation channels are promising candidates to regain channel function in acquired or inherited channelopathies. (aspetjournals.org)
- transporter
- This large group of ion channels apparently includes families 1.A.1, 1.A.2, 1.A.3, and 1.A.4 of the TCDB transporter classification. (wikipedia.org)
- mechanism
- The mechanism that permits coordinated opening of multiple Ca v 1.2 channels during EC-coupling, however, has not yet been elucidated. (washington.edu)
- physiological
- In light of the broad range of physiological roles of cation channels, it is not surprising that channel impairment results in a variety of pathophysiological conditions. (aspetjournals.org)
- passage
- Furthermore, in some ion channels, the passage is governed by a gate which is controlled by chemical or electrical signals, temperature, or mechanical forces. (bertin-bioreagent.com)
- Current
- The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and is activated by retigabine, a novel anti-convulsant drug. (bertin-bioreagent.com)
- diseases
- The fruits of these collaborations include recognition that diseases caused by ion channel dysfunction may have genetic and autoimmune aetiologies. (bmj.com)
- known
- The position of these arginines, known as gating arginines, are highly conserved in all voltage-gated potassium, sodium, or calcium channels. (wikipedia.org)
- The known specificity of these drugs strongly suggested that this 4-AP and TEA-sensitive conductance is mediated by Kv3 potassium channels. (50webs.com)
- activation
- In addition, the most common treatments for asthma, β-adrenergic agonists, apparently confer much of their effects through activation of large conductance Ca 2+ -activated (BK-type) K + channels ( Kotlikoff and Kamm, 1996 ). (frontiersin.org)
- influencing ion channel function
- Other factors influencing ion channel function include intracellular messengers, phosphorylation of channel residues, pH, and temperature. (bmj.com)
- conductance
- It was found that potassium conductance highly sensitive to external TEA (1 mM ) or 4-aminopyridine (4-AP, 200 μM) is responsible for fast repolarization and afterhyperpolarization of a single AP, providing the cells with the ability for high-frequency firing. (50webs.com)
- Potassium conductance sensitive to α- dendrotoxin (α-DTX, 100 nM ) did not play such a role. (50webs.com)