Logged in as a Visitor.
potassium voltage-gated channel, KQT-like subfamily, member 2
KV7.2 is also known as: KCNQ2; EBN; BFNC; EBN1; ENB1; BFNS1; EIEE7; HNSPC; KCNA11; KVEBN1
The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by KCNQ2 and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1) . At least five transcript variants encoding five different isoforms have been found for this gene. See  for a review paper.
Kcnq2 : potassium voltage-gated channel, KQT-like subfamily, member 2
Calmodulin bound to KCNQ2 acts as a Ca2+ sensor, conferring Ca2+ dependence to the trafficking of the channel to the plasma membrane. 
Syntaxin 1A expressed with KCNQ2 homomeric channels resulted in a 2-fold reduction in macroscopic conductance and 2-fold slower activation kinetics.
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. 
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. 
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. 
STRUCTURE & MUTATION OF Kv7.2
Basic structure of KCNQ2/3 proteins and mutations leading to BFNC. KCNQ proteins have six transmembrane domains (TMDs) and a pore-forming P-loop. Mutations found in KCNQ2 (blue circles): Y284C, A306T, fs283, fs494 and spl516, spl397, fs534, fs616 and fs838. Numbering of KCNQ2 residues is according to KCNQ3 mutations (green squares). Several mutations truncate the channel before or in the A domain or the putative assembly domain, shown as beige and white boxes respectively. KCNQ4 mutations (red squares) identified in people with progressive dominant hearing loss DFNA2. With the exception of Fs71, these mutants exert dominant-negative effects. The L281S mutation73 has not been tested functionally. The equivalent tryptophan residue is mutated in KCNQ3 (W309R) and KCNQ4 (W276S), as well as in KCNQ1 in JLNS (W305S)74, indicating that it has no strong dominant-negative effect. G285 is the first glycine of the GYG pore signature sequence, which is also mutated in KCNQ1 in the dominant long-QT syndrome (G314S)75and suppresses wild-type KCNQ1 currents. Fs, frameshift mutation; spl, splice site mutation. Both types of mutations are expected to truncate the protein. c | Dendrogram of KCNQ and selected Kv channels 
Like all Kv channels, the KCNQ α subunits share a common core structure of six transmembrane segments with a voltage sensing domain (S1–S4) and a pore domain (S5 and S6). Sequence analysis predicts the presence of four helical regions (A–D) in all family members , and helices A and B constitute the binding site for calmodulin (CaM).  See figure 1 in  for the basic structure of KCNQ2/3 channels.
Mutation of the putative Gly hinge to Ala in KCNQ2 (Kv7.2) stops channel function.
DISTRIBUTION OF KCNQ2 in NEURON
KCNQ2 (but not KCNQ3) neuropil staining also was detected in the inner, but not the outer, dentate molecular layer. It is in the dentate inner molecular layer that associational fibers derived from hilar mossy cells form en passante excitatory synapses on granule cell proximal dendrites. Because the granule cell dendrites extend radially through both inner and outer molecular layers, but the mossy cell axons and terminals are restricted to the inner layer, the KCNQ2 staining in the inner molecular layer seems most likely presynaptic. Thus, at least two types of hippocampal excitatory neurons (the mossy cells and granule cells) appear to express channels containing KCNQ2 but not KCNQ3 on their axons and/or termini, where they may regulate action potential propagation and neurotransmitter release 
KCNQ2 plays a functional role at axonal initial segments and nodes of Ranvier.
M-type channels are generated by the KCNQ (Kv7) family of voltage-gated subtypes , and they are found throughout the nervous system where they fulfil dominant roles in the control of excitability and neural discharges . The M channel is slowly activating and deactivating potassium conductance important for determining the subthreshold electroexcitability in the central nervous system, especially in neocortical, thalamic, and hippo- campal neurons. Therefore, heteromers of KCNQ2 with KCNQ3 or KCNQ5 forming M-type current potassium channels play a crucial role in the modulation of neuro- nal excitability.  KCNQ2 and KCNQ3 are coexpressed on the cell bodies and dendrites of many hippocampal and cortical neurons. 
Benign Familial Neonatal Convulsions are a rare epilepsy disorder with an autosomal-dominant inheritance. It is linked to mutations in the potassium channel genes KCNQ2 and KCNQ3. These encode for Kv7.2 and Kv7.3.  KCNQ2 mutation has implications for diagnosis and prognosis of familial neonatal seizures. 
further, KCNQ2/3 play a role in idiopathic generalized epilepsies and Rolandic epilepsy. 
KCNQ2 and KCNQ3 were identified by homology to KCNQ1, and also by positional cloning in families with benign familial neonatal convulsions (BFNC), a neonatal form of epilepsy. Both subunits are expressed mainly in neuronal tissue including sympathetic ganglia, and their expression patterns in the brain overlap extensively. However, in situ hybridization indicates that they are not always expressed in the same ratio, and immunocytochemistry has shown that some neurons stain only for one or the other subunit. Both KCNQ2 and KCNQ3 can form homomeric potassium channels when expressed alone, but currents are much smaller with KCNQ3, at least in oocytes. Like KCNQ1, both KCNQ2 and KCNQ3 yield potassium currents that activate slowly on depolarization. 
KCNQ2/KCNQ3 heteromers yield currents with the properties of the M-current, see figure 2 in Jentsch's review .
Single Channel Kv7.2 Currents in CHO cells
Interestingly, celecoxib, a COX-2-specific inhibitor, has been shown to enhance Kv7.2–Kv7.5 currents overexpressed in HEK 293 cells with an EC50 of 2–5 µM. Previously, celecoxib had been shown to enhance Kv7.5 currents in A7r5 rat aortic smooth muscle cells and cause a vasodilatation of rat mesenteric arteries, whereas other COX-2-specific inhibitors, such as rofecoxib (Vioxx™; Merck & Co. Inc., Whitehouse Station, NJ, USA), had no effect on the currents 
Editor : Admin.
Contributors : Rajnish Ranjan, Michael Schartner, Nitin Khanna
To cite : [Editor], [Contributors]. Accessed on [Date] Channelpedia , http://channelpedia.epfl.ch/ionchannels/24