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)
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)
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)
20011
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)
Subfamily1
Voltage-gated potassium (Kv) channels in the KCNQ (Kv7) subfamily are highly influential in the nervous system, muscle and epithelia. (bvsalud.org)
KCNQ2
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)
Currents3
We found that gintonin enhances I Ks channel currents in concentration- and voltage-dependent manners. (molcells.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)
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)
Membrane1
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)
Regulation2
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)
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)
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)
KCNE13
The slowly activating delayed rectifier K + ( I Ks ) channel is a cardiac K + channel composed of KCNQ1 and KCNE1 subunits. (molcells.org)
In the heart, KCNQ1 associates with KCNE1 subunits to form I Ks channels that regulate heart rhythm. (elifesciences.org)
KCNE1 suppresses the IO state so that the I Ks channel opens only to the AO state. (elifesciences.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)
Activity1
However, gintonin had no effect on hERG K + channel activity. (molcells.org)
Activation1
Gintonin-mediated activation of both the I Ks channel was also blocked by the calmodulin (CaM) blocker calmidazolium. (molcells.org)
Results1
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)
Proteins3
Some of these loci have been identified further as specific mutations in the KCNQ2 and KCNQ3 M-type potassium channel proteins. (medscape.com)
The calcium acts as an intracellular messenger by activating calcium-responsive proteins. (lookformedical.com)
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)
Seizures1
Given the severity of the impairment to the M-type potassium channel, that these seizures are difficult to treat is not surprising, because no currently used antiepileptic medications are known to increase the efficiency of the potassium channel. (medscape.com)
Neurons2
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)
Expression of the mutated genes in xenopusoocytes has provided some insight into how the potassium channel mutation leads to lowering of the seizure threshold. (medscape.com)
Properties1
LRRC8 amino-termini influence pore properties and gating of volume-regulated VRAC anion channels. (neurotree.org)
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)
The potassium current was reduced in the channel expressed by the mutated gene to 5% of that in the channel expressed by the normal gene. (medscape.com)