Voltage-gated potassium (Kv) channels in the KCNQ (Kv7) subfamily are highly influential in the nervous system, muscle and epithelia. (bvsalud.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)
KCNQ7
Through large-scale analysis of 897 patients with gastro-oesophageal adenocarcinomas (GOAs) coupled with in vitro models, we find KCNQ family genes are mutated in ∼30% of patients, and play therapeutically targetable roles in GOA cancer growth. (life-science-alliance.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 potassiumions, 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)
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)
Pore domain1
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)
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 brainsodium channels are observed on expression in Xenopusoocytes, Chinese hamster lung and ovary cells, and human embryonic kidney cells (Isom et al. (jneurosci.org)
Conduction2
There are commonly additional regulatory domains which serve to regulate ion conduction and channel gating. (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)
Neuronal2
To investigate the effects of loss of β1 function in vivo , we have used gene-targeting methods to produce β1(-/-) mice, and we have analyzed their neuronal phenotypes. (jneurosci.org)
Hyperpolarization-activated cation channels (HCN) are involved in neuronal pacemaker activity and regulate neuronal excitability through hyperpolarization-activated I h current. (epilepsygenetics.net)
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)
Mechanism1
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)
Regulate1
In the heart, KCNQ1 associates with KCNE1 subunits to form I Ks channels that regulate heart rhythm. (elifesciences.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 Xenopusoocytes. (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)
K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. (modeldb.science)
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)
Activation2
Gintonin-mediated activation of both the I Ks channel was also blocked by the calmodulin (CaM) blocker calmidazolium. (molcells.org)
Activation of mAChRs is relatively slow (milliseconds to seconds) and, depending on the subtypes present (M1-M5), they directly alter cellular homeostasis of phospholipase C, inositol trisphosphate, cAMP, and free calcium. (genome.jp)
Important2
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)
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)
Domains1
where heterotetramers may be encoded as distinct genes or as multiple pore domains within a single polypeptide. (wikipedia.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)