User Visitor Login
English only
EPFL > FSV > BBP > Channelpedia
Ion channels
Logged in as a Visitor.


potassium voltage-gated channel, KQT-like subfamily, member 3
Synonyms: KV7.3 EBN2 BFNC2 KCNQ3. Symbol: Kcnq3


The potassium voltage-gated channel KQT-like subfamily member 3, Kv7.3 is also known as KCNQ3; EBN2; BFNC2; FLJ37386; FLJ38392; DKFZp686C0248.

Voltage-gated KCNQ (Kv7) potassium channels are of critical importance in excitable tissue [464]. In the nervous system, KCNQ2 and KCNQ3 subunits are the main component of the M-current [695], [700], which is a voltage-dependent, non-inactivating potassium current that plays a central role in integrating activity of both peripheral and central neurons. From an evolutionary perspective, KCNQ2 and KCNQ3 were the last KCNQ subunits to emerge, coincident with the apparition of myelin [701].

KCNQ2/KCNQ3 channels are the molecular correlates of the neuronal M-channels, which play a major role in the control of neuronal excitability.[58] The M-channel was first described in 1980 by [465] according to [464].


KCNQ3 is unusual because it has an alanine in the inner vestibule, three residues upstream of the signature GYG (see Fig.1A in [698]).

Kcnq3 : potassium voltage-gated channel, KQT-like subfamily, member 3

RGD ID Chromosome Position Species
69222 7 103325185-103627045 Rat
735596 15 65826477-66117786 Mouse
735595 8 133141256-133493004 Human


Acc No Sequence Length Source
NM_031597 NCBI
NM_152923 NCBI
NM_004519 NCBI


Accession Name Definition Evidence
GO:0008076 voltage-gated potassium channel complex A protein complex that forms a transmembrane channel through which potassium ions may cross a cell membrane in response to changes in membrane potential. IEA
GO:0016020 membrane Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins. IEA
GO:0016021 integral to membrane Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane. IEA


M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a anti-convulsant drug. (

Expression of KCNQ2 and KCNQ3 individually yields only small currents, whereas their coexpression yields heteromeric currents 10-fold larger [695].

Extracellular H+ ions

Whole-cell and single-channel recordings demonstrated that extracellular H+ ions effect heterologously expressed KCNQ2/3 channels in the following way: KCNQ2/3 current was inhibited by H+ ions with an IC50 of 52 nM (pH 7.3) at -60 mV, rising to 2 microM (pH 5.7) at -10 mV. Neuronal M-current exhibited a similar sensitivity. I.e. extracellular H+ ions affected two distinct properties of KCNQ2/3 current: the maximum current attainable upon depolarization (Imax) and the voltage dependence of steady-state activation. [66]

Mepyramine and Diphenhydramine

Mepyramine and diphenhydramine, two structurally related first-generation antihistamines, can act as potent KCNQ/M channel blockers. Extracellular application of these drugs quickly and reversibly reduced KCNQ2/Q3 currents heterologously expressed in HEK293 cells. [72]

Hydroxyl-Containing Residue at the 315 Position

Most of the wild-type KCNQ3 homomers, being well expressed at the plasma membrane, are functionally silent. Rearrangements of the pore-loop architecture induced by the presence of a hydroxyl-containing residue at the 315 position unlocks the channels into a conductive conformation. [73]

Meclofenamate and Diclofenac

Meclofenamic acid (meclofenamate) and diclofenac, two related molecules previously used as anti-inflammatory drugs, act as KCNQ2/Q3 channel openers. Extracellular application of meclofenamate (EC(50) = 25 microM) and diclofenac (EC(50) = 2.6 microM) resulted in the activation of KCNQ2/Q3 K(+) currents by causing a hyperpolarizing shift of the voltage activation curve and markedly slowing the deactivation kinetics. The effects of the drugs were stronger on KCNQ2 than on KCNQ3 channel alpha subunits but they did not enhance KCNQ1 K(+) currents. Both openers increased KCNQ2/Q3 current amplitude at physiologically relevant potentials and led to hyperpolarization of the resting membrane potential. [78]


KCNE1 slowed KCNQ2/3 currents and decreased their magnitude [1680]. However no significant effects have also been recorded when KCNE1 was co-expressed at levels that suffice to alter KCNQ1. An interaction of KCNQ2/3 with either KCNQ1 or KCNE1 would also seem physiologically irrelevant as neither has been detected in the CNS [704]


Native M-channels and expressed Kv7.2 + 7.3 channels are inhibited by stimulating Gq/11-coupled receptors – prototypically the M1 muscarinic acetylcholine receptor (M1-mAChR). The channels require membrane phosphatidylinositol-4,5-bisphosphate (PIP2) to open and the effects of mAChR stimulation result primarily from the reduction in membrane PIP2 levels following Gq/phospholipase C-catalysed PIP2 hydrolysis. However, in sympathetic neurons, M-current inhibition by bradykinin appears to be mediated through the release and action of intracellular Ca2+ by inositol-1,4,5-trisphosphate (IP3), a product of PIP2 hydrolysis, rather than by PIP2 depletion [1744]



It is generally thought that KCNQ2/3 surface expression is governed by the intracellular C-terminal region, and that the pore region does not have any significant role in trafficking [705], [707], [708], [709], [73]. Basic structure of KCNQ2/3 proteins can be seen in figure 1 of [464]


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]



Kv7.1 structure

In the hippocampal formation and cerebral cortex, KCNQ2 and KCNQ3 staining was detected on the somata and dendrites of many polymorphic and pyramidal neurons. Confocal immunofluorescence microscopy revealed that this somatodendritic staining was punctate in character and appeared to label both the cell surface and intracellular components ​(C). In the hippocampal formation, hilar polymorphic cells. ​( E and H), CA3 pyramidal cells (F), and subicular pyramidal cells ​(G) exhibited somatodendritic staining for both subunits.

KCNQ2 and KCNQ3 proteins are colocalized in a somatodendritic pattern on pyramidal and polymorphic neurons in the human cortex and hippocampus. Immunoreactivity for KCNQ2, but not KCNQ3, is also prominent in some terminal fields, suggesting a presynaptic role for a distinct subgroup of M-channels in the regulation of action potential propagation and neurotransmitter release [1681]

The KCNQ2/3 subunits acquired an ankyrin G-binding motif, that allows them to concentrate at the nodes of Ranvier and the axonal initial segment (AIS) [702], [703]. KCNQ3 is a major determinant of M-channels location to the AIS [703] and displays a predominant intracellular distribution, whereas its combination with KCNQ2 leads to a large increase in axonal surface expression [706].


KCNQ2 and KCNQ3 are coexpressed on the cell bodies and dendrites of many hippocampal and cortical neurons. [461]


Spontaneous mutations in Kv7.3, some producing a mere 25% reduction in function, cause human neonatal epilepsy [704], [705].

KCNQ2 and KCNQ3 play an important role in neonatal epilepsy. [462]


Mutations causing benign familial neonatal convulsions were found to cause only slight reductions in current compared with wild-type controls, suggesting that small differences in the activity of these KCNQ channels in vivo might be sufficient to cause epilepsy [704]


KCNQ2/KCNQ3 (See also Kv7.2 for more info)

KCNQ2/KCNQ3 heteromers yield currents with the properties of the M-current, see figure 2 in [464].

Mutations in either KCNQ2 or KCNQ3 can cause the same phenotype (BFNC), and the expression of both subunits overlaps extensively, so they may combine to form a single channel. Expression of both subunits leads to larger currents with slightly changed gating kinetics and sensitivity to inhibitors. Furthermore, a KCNQ3 mutant modelled on a dominant-negative KCNQ1 mutation found in RWS inhibited KCNQ2 currents in a DOMINANT-NEGATIVE fashion [704]


Single-channel and noise analysis indicated that homomeric KCNQ2 and KCNQ3 channels have conductances of roughly 18 and 7 pS, respectively. Co-expression did not increase the single-channel conductance, which varied between 8 and 22 ps. This variation suggested the formation of heteromers with different stoichiometries [463]

KCNQ2/3 in CHO cells

Kv7.1 structure We used coexpression of GFP as a reporter for successful transfection, and only cells that fluoresced green were chosen for study using whole-cell clamp. CHO cells transfected with KCNQ2 and KCNQ3 expressed voltage-gated K+ currents with slow activation kinetics typical of KCNQ channels (Fig.1 A), whereas nontransfected CHO cells had negligible macroscopic K+ currents [68]



[604 : 20628086]
[698 : 20610766]
[699 : 20379614]
[605 : 19913121]
[694 : 19464834]
[464 : 11252765]
[700 : 12356878]
[701 : 19112491]
[702 : 16525039]
[703 : 17311847]
[705 : 12640002]
[706 : 16735477]
[695 : 9836639]
[707 : 10788442]
[708 : 15483133]
[709 : 18440995]
[58 : 19675672]
[59 : 18272489]
[60 : 15901787]
[66 : 14638935]
[67 : 12524525]
[69 : 11466425]
[70 : 10713961]
[461 : 9074774]
[72 : 18222495]
[73 : 18790849]
[462 : 11572947]
[78 : 15598972]
[463 : 19298256]
[465 : 6965523]
[1680 : 9677360]
[704 : 9872318]
[1681 : 10781098]
[1744 : 17395626]
[68 : 12514204]


Editor : Admin.

Contributors : Rajnish Ranjan, Michael Schartner

To cite : [Editor], [Contributors]. Accessed on [Date] Channelpedia ,