SubfamilySubunitKCNQKineticsConductionTransmembraneProteinsMechanismCurrentsXenopusHippocampalRegulateRegulationKCNQ1ReceptorKCNE1BrainEffectsCellFoundPlayActivationActionSubunitsPoreNotablyMembraneACTION POTENTIALSSelectiveFunctionalToxinsExcitableMutationsInsightsNeuronsNeurologicalMechanismsCellularMarkersBrainCellsIncreaseDiseaseGroupDevelopment
Subfamily2
- Voltage-gated potassium (Kv) channels in the KCNQ (Kv7) subfamily are highly influential in the nervous system, muscle and epithelia. (bvsalud.org)
- The KCNQ (potassium voltage-gated channel subfamily Q) family of ion channels encode potassium transporters ( 1 ). (life-science-alliance.org)
Subunit5
- These results show that gintonin-mediated enhancement of I Ks channel currents is achieved through binding of the [Ca 2+ ] i /CaM complex to the C terminus of KCNQ1 subunit. (molcells.org)
- Channels formed from KCNQ proteins consist of homomeric tetramers or heteromeric tetramers containing KCNQ as the α-subunit, and each KCNQ subunit is composed of six α-helical transmembrane segments (S1-S6). (molcells.org)
- It adopts the canonical structural organization of the homo-tetrameric K V superfamily, in which each subunit contains six transmembrane segments (S1-S6), with the first four (S1-S4) forming the voltage-sensing domain (VSD) and the latter two (S5-S6) folding to the pore ( Sun and MacKinnon, 2017 ). (elifesciences.org)
- Functionally, the two open states have different gating properties and are differentially modulated by the auxiliary subunit KCNE1, allowing us to experimentally distinguish them. (elifesciences.org)
- Sodium channel β1 subunits modulate α subunit gating and cell surface expression and participate in cell adhesive interactions in vitro . (jneurosci.org)
KCNQ6
- The KCNQ family of channel proteins (also known as Kv7) form K + -selective, voltage-gated channels ( Hille, 2001 ) that are slowly activating delayed rectifier K + ( I Ks ) channels. (molcells.org)
- Four members of the KCNQ family are neuronal (KCNQ2-5), and one (KCNQ1) is expressed in cardiac tissue. (molcells.org)
- KCNQ channel proteins also co-assemble with KCNE1-4 subunits ( McCrossan and Abbott, 2004 ). (molcells.org)
- We also discover that activity of KCNQ3 sensitises cancer cells to existing potassium channel inhibitors and that inhibition of KCNQ activity reduces proliferation of GOA cancer cells. (life-science-alliance.org)
- These findings reveal a novel and exploitable role of potassium channels in the advancement of human cancer, and highlight that supplemental treatments for GOAs may exist through KCNQ inhibitors. (life-science-alliance.org)
- KCNQ proteins typically repolarise the plasma membrane of a cell after depolarisation by allowing the export of potassium ions, and are therefore involved in wide-ranging biological functions including cardiac action potentials ( 2 ), neural excitability ( 3 ), and ionic homeostasis in the gastrointestinal tract ( 4 ). (life-science-alliance.org)
Kinetics1
- However, the effects of β1 are highly dependent on the experimental system in which they are studied, and different effects on the kinetics and voltage dependence of gating of brain sodium channels are observed on expression in Xenopus oocytes, Chinese hamster lung and ovary cells, and human embryonic kidney cells (Isom et al. (jneurosci.org)
Conduction3
- There are commonly additional regulatory domains which serve to regulate ion conduction and channel gating. (wikipedia.org)
- 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)
- Our results show that β1 subunits play important roles in the regulation of sodium channel density and localization, are involved in axo-glial communication at nodes of Ranvier, and are required for normal action potential conduction and control of excitability in vivo . (jneurosci.org)
Transmembrane4
- 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)
- Sridhar A, Lummis SCR, Pasini D, Mehregan A, Brams M, Kambara K, Bertrand D, Lindahl E, Howard RJ, Ulens C ( 2021 ) A cationic lipid site at the outward transmembrane face of a pentameric ligand-gated ion channel. (multichannelsystems.com)
Proteins1
- Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca 2+ ] i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. (molcells.org)
Mechanism2
- These observations support a distinctive mechanism responsible for the VSD-pore coupling at the AO state that is sensitive to ML277 modulation. (elifesciences.org)
- ML277 provides insights and a tool to investigate the gating mechanism of KCNQ1 channels, and our study reveals a new strategy for treating long QT syndrome by specifically enhancing the AO state of native I Ks currents. (elifesciences.org)
Currents2
- We found that gintonin enhances I Ks channel currents in concentration- and voltage-dependent manners. (molcells.org)
- Sodium currents in dissociated hippocampal neurons are normal, but Na v 1.1 expression is reduced and Na v 1.3 expression is increased in a subset of pyramidal neurons in the CA2/CA3 region, suggesting a basis for the epileptic phenotype. (jneurosci.org)
Xenopus3
- In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I Ks channel activity by expressing human I Ks channels in Xenopus oocytes. (molcells.org)
- In the present study, we used the Xenopus oocyte gene expression system to investigate the molecular mechanisms underlying how gintonin-mediated [Ca 2+ ] i transients are coupled to the regulation of I Ks channel activity. (molcells.org)
- Here, we tested modulations of human KCNQ1 channels by an activator ML277 in Xenopus oocytes. (elifesciences.org)
Hippocampal1
- K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. (modeldb.science)
Regulate1
- In the heart, KCNQ1 associates with KCNE1 subunits to form I Ks channels that regulate heart rhythm. (elifesciences.org)
Regulation1
- Sridhar A, Lummis SCR, Pasini D, Mehregan A, Brams M, Kambara K, Bertrand D, Lindahl E, Howard RJ, Ulens C ( 2021 ) Regulation of a pentameric ligand-gated ion channel by a semi-conserved cationic-lipid binding site. (multichannelsystems.com)
KCNQ14
- The slowly activating delayed rectifier K + ( I Ks ) channel is a cardiac K + channel composed of KCNQ1 and KCNE1 subunits. (molcells.org)
- The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I Ks channels. (molcells.org)
- Mutations in the KCNQ1 [Ca 2+ ] i /CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I Ks channel. (molcells.org)
- Upon membrane depolarization, the KCNQ1 potassium channel opens at the intermediate (IO) and activated (AO) states of the stepwise voltage-sensing domain (VSD) activation. (elifesciences.org)
Receptor1
- Gintonin-mediated activation of the I Ks channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP 3 receptor antagonist, and the calcium chelator BAPTA. (molcells.org)
KCNE11
- KCNE1 suppresses the IO state so that the I Ks channel opens only to the AO state. (elifesciences.org)
Brain1
- KCNQ2, KCNQ3, KCNQ4, and KCNQ5, however, can interact with each other and the KCNE family to theoretically form hundreds of combinations of channels, but are predominantly found in KCNQ2/KCNQ3 heteromers in the brain. (life-science-alliance.org)
Effects2
- These results suggest that effects of β1 on sodium channel gating are dependent on the genetic background and signal transduction pathways present in the cell type used in heterologous expression and emphasize the importance of analyzing the effects of β1 in vivo . (jneurosci.org)
- These potential effects on channel gating and subcellular distribution in vivo may bias neurons toward hyperexcitability and epileptogenesis. (jneurosci.org)
Cell1
- β1 subunits affect sodium channel gating and cell surface expression when expressed in heterologous cells in vitro . (jneurosci.org)
Found1
- This also includes the 2-TM inward-rectifier potassium channels (Pfam PF01007) found primarily in eukaryotes. (wikipedia.org)
Play2
- These results suggest that, as channel modulators, β subunits play important roles in control of electrical signaling and, as CAMs, β subunits act as critical communication links between extracellular and intracellular signaling molecules. (jneurosci.org)
- Voltage-sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. (life-science-alliance.org)
Activation1
- Gintonin-mediated activation of both the I Ks channel was also blocked by the calmodulin (CaM) blocker calmidazolium. (molcells.org)
Action2
- In the optic nerve, the fastest components of the compound action potential are slowed and the number of mature nodes of Ranvier is reduced, but Na v 1.6, contactin, caspr 1, and K v 1 channels are all localized normally at nodes. (jneurosci.org)
- Moreover, we reveal that, in male and female rats, this action depends on M-like potassium conductance. (jneurosci.org)
Subunits4
- Instead, this review is focused on the genetic neuronal ion channel disorders and specifically, those inherited or de novo mutations in ion channel subunits that result in brain dysfunction. (acnr.co.uk)
- Mutations in genes which encode subunits of CNS sodium, potassium, calcium channels, GABAA and nicotinic receptors have been reported in association with various epilepsy syndromes 2-3 (Table 1). (acnr.co.uk)
- KCNT1 and KCNT2 respectively encode the K Na 1.1 (Slack) and K Na 1.2 (Slick) subunits of the sodium-dependent voltage-gated potassium channel K Na . (frontiersin.org)
- These subunits co-assemble to form homo or tetra-heteromeric K Na channels. (frontiersin.org)
Pore2
- They are described as minimally having two transmembrane helices flanking a loop which determines the ion selectivity of the channel pore. (wikipedia.org)
- LRRC8 amino-termini influence pore properties and gating of volume-regulated VRAC anion channels. (neurotree.org)
Notably2
- notably, they decreased the global current density of heteromeric channels by ~25% (p.K564*) and ~55% (p.L48Qfs43). (frontiersin.org)
- Dysfunction of potassium channels has notably been involved in various types of epileptic encephalopathies, including epilepsy of infancy with migrating focal seizures (EIMFS), previously known as malignant migrating partial seizures of infancy. (frontiersin.org)
Membrane4
- Altered transcription, assembly, and membrane trafficking of ion channels may also contribute to many acquired neurological ion channel disorders. (acnr.co.uk)
- Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. (lookformedical.com)
- The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. (lookformedical.com)
- Cell membrane glycoproteins that form channels to selectively pass chloride ions. (lookformedical.com)
ACTION POTENTIALS1
- Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. (lookformedical.com)
Selective5
- Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. (jneurosci.org)
- A class of drugs that act by selective inhibition of calcium influx through cellular membranes. (lookformedical.com)
- Gated, ion-selective glycoproteins that traverse membranes. (lookformedical.com)
- Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. (lookformedical.com)
- Gating is thought to involve conformational changes of the ion channel which alters selective permeability. (lookformedical.com)
Functional2
- Functional analyses of the corresponding mutant homomeric channels in vitro suggested gain-of-function effects. (frontiersin.org)
- Using whole-cell patch-clamp recordings, we have analyzed the functional consequences of those two novel KCNT2 mutations on reconstituted K Na 1.2 homomeric and K Na 1.1/K Na 1.2 heteromeric channels in transfected chinese hamster ovary (CHO) cells. (frontiersin.org)
Toxins2
- Acquired channelopathies are generally caused by antibodies that target specific ion channels or by toxins and venoms which block voltage-gated ion channels. (acnr.co.uk)
- Omega toxins inhibit the actions of these channels by altering their voltage dependence. (lookformedical.com)
Excitable2
- Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. (lookformedical.com)
- Agents that increase calcium influx into calcium channels of excitable tissues. (lookformedical.com)
Mutations1
- The last two decades have witnessed a rapid increase in the number of inherited disorders caused by ion channel mutations. (acnr.co.uk)
Insights1
- Overall our data emphasize the involvement of KCNT2 in EOEE and provide novel insights into the role of heteromeric K Na channel in the severe KCNT2 -related epileptic phenotypes. (frontiersin.org)
Neurons3
- In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. (jneurosci.org)
- CALCIUM CHANNELS located in the neurons of the brain. (lookformedical.com)
- K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. (modeldb.science)
Neurological1
- Among this expanding group, neurological ion channel disorders are among the best characterised, reflecting the fundamental importance of electrical excitability in the membranes of nerve and muscle cells. (acnr.co.uk)
Mechanisms1
- Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. (lookformedical.com)
Cellular1
- Cellular basis of ClC-2 Cl channel-related brain and testis pathologies. (neurotree.org)
Markers1
- Dihydropyridine-based calcium antagonists are used as markers for these binding sites. (lookformedical.com)
Brain2
- Genetic ion channel disorders of the brain generally manifest as epilepsy, migraine, paroxysmal dyskinesia, or episodic ataxia. (acnr.co.uk)
- Whilst a comprehensive review of the brain ion channel disorders is beyond the ambition of this article, our aim is to provide a brief overview of the field and consider the most recent advances, especially from a mechanistic point of view. (acnr.co.uk)
Cells3
- The largest group of neocortical inhibitory interneurons (∼50%) consists of cells that contain the calcium-binding protein parvalbumin (PV). (jneurosci.org)
- CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. (lookformedical.com)
- Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity. (neurotree.org)
Increase1
- K Na channels are voltage-gated potassium channels that are activated by an increase of cytoplasmic Na + concentration. (frontiersin.org)
Disease1
- It was the first epilepsy disorder for which gene linkage studies established a disease locus, and subsequently identified a pair of potassium channel genes that had not previously been cloned. (acnr.co.uk)
Group2
- 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)
- A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. (lookformedical.com)
Development1
- LRRC8/VRAC anion channels are required for late stages of spermatid development in mice. (neurotree.org)