Channelpedia

Kv7

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Introduction

The KCNQ gene family encodes Kv7 channel subunits that form homo- or heteromeric Kv7 channels (also termed M-channels) which represent the molecular correlate to the M-current [695].

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Gene

Underlain by the KCNQ family of genes [695], M channels, also known as Kv7 [760]

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Structure

KCNQ STRUCTURE

KCNQ proteins have six transmembrane domains and are structurally related to Kv potassium channels. The degree of homology between different KCNQ proteins is less than that observed within Kv family branches (for example, within Kv1 channels). Like other Kv channels, KCNQ subunits have a single P-loop that forms the selectivity filter of the pore (in four copies provided by four subunits), a positively charged fourth transmembrane domain (S4) that probably acts as a voltage sensor, and intracellular amino and carboxy termini. The C terminus is quite long, and contains a conserved domain (the 'A domain'24) closely followed by a short stretch thought to be involved in subunit assembly, at least in KCNQ1 [463]

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Kinetics

KCNQ General Kinetics

Kv7 subtypes start opening at around −60 mV (although the voltage dependency of Kv7 channels differ between heterologous and native cells), thus being functionally active close to the resting membrane potential. In addition, Kv7 channels may be considered as being non-inactivating (‘leaky’) K+ channels at physiologically relevant resting potentials, although a proportion of Kv7 channels may undergo steady-state inactivation [712]. These characteristics enable the Kv7 channels to produce the underlying subthreshold M-current, which stabilizes the neuronal resting potential. Consequently, the Kv7 channels are thought to inhibit neuronal excitability and put a ‘brake’ on action potential firing when the neuron is exposed to an excitatory stimulus. [752]

M Current

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]).

Brown and colleagues were the first to describe a neuronal K+ current in bullfrog sympathetic cells that they named ‘M current’ due to its suppression by stimulation of muscarinic acetylcholine receptors (mAChRs) [465]. This time- and voltage-dependent K+ current has a threshold for activation at typical neuronal resting potentials, with greater activity upon depolarization. This characteristic and its lack of inactivation give M current a major impact on neuronal excitability. Suppression of M current by the activation of appropriate receptors or by pharmacological blockade allows neurons to fire more rapidly due to the reduction in accommodation or spike frequency adaptation [758], [695], [759].

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Biophysics

Model Km1 (ID=15)      

AnimalN.A
CellType N.A
Age 0 Days
Temperature0.0°C
Reversal -84.0 mV
Ion K +
Ligand ion
Reference [268] A Bibbig et. al; J. Neurosci. 2001 Nov 15
mpower 1.0
m Alpha 0.02/(1+exp((40-v)/5))
m Beta 0.01*exp((17-v)/18)

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Model Km2 (ID=16)      

Original Kfast model

AnimalN.A
CellType N.A
Age 0 Days
Temperature0.0°C
Reversal -84.0 mV
Ion K +
Ligand ion
Reference [269] Roger D Traub et. al; J. Neurophysiol. 2003 Feb
mpower 1.0
m Alpha 0.02/(1+exp((-v-20)/5))
m Beta 0.01*exp((-v-43)/18)

MOD - xml - channelML

Model Km3 (ID=17)      

AnimalN.A
CellType N.A
Age 0 Days
Temperature0.0°C
Reversal -84.0 mV
Ion K +
Ligand ion
Reference [270] D Johnston et. al; J. Neurophysiol. 1995 Mar
mpower 1.0
m Alpha 0.006*exp(10*0.06*(v+55)*0.04)
m Beta 0.06*exp(-9.4*(v+55)*0.04)

MOD - xml - channelML

Model Im (ID=47)      

AnimalBullfrog
CellType Neurons
Age 0 Days
Temperature0.0°C
Reversal -85.0 mV
Ion K +
Ligand ion
Reference [1498] D A Brown et. al; J. Physiol. (Lond.) 1982 Sep
mpower 1.0
m Alpha 3.3e-3 * exp(2.5 * 0.04*(v - -35))
m Beta 3.3e-3 * exp(-2.5 * 0.04 *(v - -35))

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Expression and Distribution

Kv isoforms are localized throughout the nervous system [695],[702],

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Interaction

Kv7 channels are inhibited by stimulation of a variety of Gq/11 -coupled neurotransmitter receptors. [751]

References

136

Schrøder RL et al. KCNQ4 channel activation by BMS-204352 and retigabine.
Neuropharmacology, 2001 Jun , 40 (888-98).

461

Marrion NV Control of M-current.
Annu. Rev. Physiol., 1997 , 59 (483-504).

463

Brown DA et al. Neural KCNQ (Kv7) channels.
Br. J. Pharmacol., 2009 Apr , 156 (1185-95).

465

Brown DA et al. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone.
Nature, 1980 Feb 14 , 283 (673-6).

695

Wang HS et al. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.
Science, 1998 Dec 4 , 282 (1890-3).

712

Jensen HS et al. Inactivation as a new regulatory mechanism for neuronal Kv7 channels.
Biophys. J., 2007 Apr 15 , 92 (2747-56).

751

Hernandez CC et al. Regulation of neural KCNQ channels: signalling pathways, structural motifs and functional implications.
J. Physiol. (Lond.), 2008 Apr 1 , 586 (1811-21).

752

Hansen HH et al. Kv7 channels: interaction with dopaminergic and serotonergic neurotransmission in the CNS.
J. Physiol. (Lond.), 2008 Apr 1 , 586 (1823-32).

1498

Adams PR et al. M-currents and other potassium currents in bullfrog sympathetic neurones.
J. Physiol. (Lond.), 1982 Sep , 330 (537-72).

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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/213/ , accessed on 2024 Nov 21


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