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Kv7.5

potassium voltage-gated channel, KQT-like subfamily, member 5
Synonyms: Kv7.5 KCNQ5. Symbol: Kcnq5

Introductions


The potassium voltage-gated channel KQT-like subfamily member 5, Kv7.5, is also known as KCNQ5.

This gene is a member of the KCNQ potassium channel gene family that is differentially expressed in subregions of the brain and in skeletal muscle. The protein encoded by this gene yields currents that activate slowly with depolarization and can form heteromeric channels with the protein encoded by the KCNQ3 gene. Currents expressed from this protein have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. Multiple transcript variants encoding different isoforms have been found for this gene.

(http://www.ncbi.nlm.nih.gov/pubmed?Db=gene&Cmd=retrieve&dopt=fullreport&listuids=56479)

M currents are a subset of native K+ currents recorded from various neurones such as sympathic, hippocampal and cortical neurones (Marrion, 1997 [461]). These currents are voltage-dependent currents activated by depolarisation, they are non-inactivating, blocked by muscarinic M1 receptor stimulation and serve to stabilize the membrane potential, and thus, reduce neuronal excitability. KCNQ channels have been suggested to be the molecular counterpart of the M channel and M-like channels (Wang et al., 1998 [695]; Schroeder et al., 2000 [136]). KCNQ2 – 5 channel subunits might combine to produce different variants of M current in different parts of the nervous system. (depuis [138])

The gene KCNQ5 (also known as Kv7.5) encodes the potassium voltage-gated channel KCNQ5, KQT-like subfamily, member 5. This gene is a member of the KCNQ potassium channel gene family that is differentially expressed in subregions of the brain and in skeletal muscle. The protein encoded by this gene yields currents that activate slowly with depolarization and can form heteromeric channels with the protein encoded by the KCNQ3 gene. Currents expressed from this protein have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. Multiple transcript variants encoding different isoforms have been found for this gene. http://www.ncbi.nlm.nih.gov/gene/56479

Genes


Kcnq5 : potassium voltage-gated channel, KQT-like subfamily, member 5

RGD ID Chromosome Position Species
1596181 9 20181877-20185273 Rat
1550963 1 21388484-21952023 Mouse
1351630 6 73331571-73908574 Human

Transcripts


Acc No Sequence Length Source
NM_001160139 NCBI
NM_023872 NCBI
NM_019842 NCBI
NM_001160130 NCBI
NM_001160132 NCBI
NM_001160133 NCBI
NM_001160134 NCBI

Ontologies


Accession Name Definition Evidence

Interactions


KCNE channel alters KCNQ5 channel gating

The proteins KCNE1 and KCNE3 alter the gating of the Kv7.5 channel in Xenopus oocytes and HEK-293 cells. While KCNE1 slows activation and inhibits inward rectification, KCNE3 inhibits the current amplitude and differentially affects activation. Furthermore, KCNE1 increases Kv7.5 currents, when co-expressed in HEK cells. [710]

Calmodulin a Calcium sensor

Compared with other Kv channels, KCNQ channels have an extended intracellular carboxyl terminus that seems to be the target of many modulatory signals. Examples are modulation by Ca2+ [716], using calmodulin as the channel Ca2+ sensor [717], and regulation by plasma membrane phosphoinositides [718], [719], [720] perhaps in concert with protein kinase C [721].

Cell volume and Zinc

Changes in cell volume, extracellular Zn2+, acidification, and muscarinic receptor activation modulate Kv7.5 [723],[724].

KCNQ3

KCNQ5 forms heteromeric channels with KCNQ3, but not with KCNQ1, KCNQ2 or KCNQ4 (Lerche et al., 2000 [140]; Schroeder et al., 2000 [724]). KCNQ5 is inhibited by the M1 muscarinic receptor activation. (Depuis [138])

KCNQ2

Co-injection of KCNQ5 with the dominant negative mutant KCNQ2(G279S) (7) or of KCNQ2 with the equivalent mutant KCNQ5(G278S) leads to a roughly 50% reduction in current amplitude, which is consistent with a lack of interaction since only 50% of WT cRNA was injected [724]

BMS-204352, a KCNQ5 activator

Anti-ischemic compound, BMS-204352, strongly activates the voltage-gated K+ channel KCNQ5 in a concentration-dependent manner with an EC50 of 2.4 micro mol. Retigabine induced a smaller, yet qualitatively similar effect on KCNQ5. Furthermore, BMS-204352 (10 mM) did not significantly shift the KCNQ5 activation curves, as observed for the other KCNQ channels. The M-current blockers, linopirdine and XE991, inhibited the activation of the KCNQ5 channel induced by the BMS-204352. (Depuis [138])

Effect of Retigabine on KCNQ3/5 heteromeric channel

Kv7.5 Retigabine induced concentration dependent leftward shifts in the KCNQ5/Q3 channel activation curve [1745]

M1 Muscarinic Inhibition

Currents expressed from KCNQ5 have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation

Linopirdine

Linopirdine has inhibitory effects on KCNQ5 [724]

TEA

Kv7.5 is poorly inhibited by the common potassium inhibitor TEA [724]

Proteins


Structures


KCNQ channels have a membrane topology similar to the Kv channels, comprising six transmembrane-spanning segments (S1 –S6) with a typical S4 domain, which is the voltage sensor, a pore loop linking S5 and S6, and intracellular N and C termini. (Dupuis [138])

Distributions


Kv7.5 Distribution in Neuron

Of its five known subunits, KCNQ5/Kv7.5 is extensively expressed in the central nervous system and it contributes to the generation of M-currents. The distribution of KCNQ5 was analyzed in auditory nuclei of the rat brainstem by high-resolution immunocytochemistry. Double labeling with anti-KCNQ5 antibodies and anti-synaptophysin or anti-syntaxin, which mark synaptic endings, or anti-microtubule-associated protein 2 (MAP2) antibodies, which mark dendrites, were used to analyze the subcellular distribution of KCNQ5 in neurons in the cochlear nucleus, superior olivary complex, nuclei of the lateral lemniscus, and inferior colliculus [1821]

Expressions


Kv7.5 expression in the Brain

This includes prominent signals in the cortex, the occipital pole, frontal and temporal lobes, the caudate putamen, and the hippocampus [724] Kv7.5 is highly expressed in skeletal muscle [715] as well as certain regions of the brain [724]. Murine vascular smooth muscle cells only express a truncated form of KCNQ5. [139]

Localization of KCNQ5 in the normal and epileptic human temporal neocortex and hippocampal formation [1822]

Kv7.5 expression in body

KCNQ5 is expressed in skeletal muscle and shows widespread expression in the central nervous system. The expression of KCNQ5 is in many brain regions overlapping with the expression of KCNQ2 and KCNQ3 (Lerche et al., 2000 [140]; Schroeder et al., 2000 [724]).

KCNQ5 gene messages were present abundantly in murine vasculature (Ohya [1092], Yeung [1093]).

Functionals


Myoblast Proliferation

Kv7.5 is involved in myoblast proliferation [714].

M current

the function of KCNQ5 in the brain remains unknown and no neurological disorders have been attributed to it. Given KCNQ5’s similar biophysical properties to other members of the KCNQ family, KCNQ5 may also contribute to M-currents [461]

The Kv7 family is unique in the sense that mutations in four of the five genes have been linked to human hereditary diseases [722], [464].

KCNQ5 channels control resting properties and release probability of a synapse

Unlike most KCNQ channels, which are activated only by depolarizing stimuli, the presynaptic channels began to activate just below the resting potential. As a result, blockers and activators of KCNQ5 depolarized or hyperpolarized nerve terminals, respectively, markedly altering resting conductance. Moreover, the background conductance set by KCNQ5 channels, together with Na(+) and hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, determined the size and time course of the response to sub threshold stimuli [1820]

Mediates after-hyperpolarization

the function of KCNQ5 (Kv7.5), which also displays widespread expression in the brain, is entirely unknown. Here, we developed mice that carry a dominant negative mutation in the KCNQ5 pore to probe whether it has a similar function as other KCNQ channels. In the CA3 area of hippocampus, a region that highly expresses KCNQ5 channels, the medium and slow afterhyperpolarization currents are significantly reduced. In contrast, neither current is affected in the CA1 area of the hippocampus, a region with low KCNQ5 expression. Our results demonstrate that KCNQ5 channels contribute to the afterhyperpolarization currents in hippocampus in a cell type-specific manner [1746]

Myogenicity and Vasodilation in the Brain

In cerebral arteries, Kv7.4 and Kv7.5 proteins exist predominantly as a functional heterotetramer, which regulates intrinsic myogenicity and vasodilation attributed to CGRP. Surprisingly, unlike systemic arteries, Kv7 activity in MCAs is not affected by the development of hypertension, and CGRP (calcitonin gene-related peptide)-mediated vasodilation is well maintained. As such, cerebrovascular Kv7 channels could be amenable for therapeutic targeting in conditions such as cerebral vasospasm [1824]

Kinetics


Human KCNQ5/Q3 in CHO cell Kinetics

Kv7.5 Representative currents from a CHO-KCNQ5Q3 cells (elicited by a series of 3-s depolarizing steps, in the range −100 to +30 mV, in 10-mV increments from a holding potential of −80 mV). [1745]



KCNQ5 Kinetics expressed in X oocytes

Kv7.5 [140] Kv7.5 [724]

Currents activated very slowly (Fig.3 A) and were not fully activated even after 3-s test pulses. At lower step potentials, KCNQ5 currents showed a delay in activation, similar to KCNQ1 currents (32). In most cells (in 23 out of 28 oocytes) activation traces above +20 mV displayed a “crossover” phenomenon, which was observed independently of current amplitudes. Activation of KCNQ5 currents was generally slower than that of other KCNQ currents. Two components of deactivation, with time constants of 51 ± 2 and 281 ± 24 ms, were observed at a repolarizing voltage of −100 mV, following a 3-s depolarizing step to +40 mV (Table I). KCNQ1 tail currents display a characteristic “hook” indicative of recovery from inactivation (32, 33). We did not observe such a feature for KCNQ5 currents at voltages between −100 and +40 mV [140]

KCNQ5 yields currents that activate slowly with depolarization. [724] (Depuis [138])

Models


References


[604 : 20628086]
[699 : 20379614]
[605 : 19913121]
[710 : 19910673]
[711 : 18786918]
[712 : 17237198]
[606 : 16382104]
[713 : 15304482]
[714 : 18331828]
[715 : 18272810]
[716 : 8562079]
[717 : 12810850]
[718 : 12165472]
[719 : 15173220]
[720 : 12670425]
[721 : 12754513]
[722 : 11448722]
[464 : 11252765]
[723 : 15963599]
[138 : 11890900]
[139 : 18457656]
[461 : 9074774]
[695 : 9836639]
[1092 : 12690036]
[1093 : 17519950]
[140 : 10787416]
[1745 : 11159685]
[724 : 10816588]
[1820 : 21666672]
[1746 : 20534576]
[1821 : 17912742]
[1822 : 12890507]
[1824 : 24558103]

Credits


Editor : Admin.

Contributors : Rajnish Ranjan, Michael Schartner

To cite : [Editor], [Contributors]. Accessed on [Date] Channelpedia , http://channelpedia.epfl.ch/ionchannels/27