M-type potassium channel (M-channel)

M-type potassium channels are low-threshold, non-inactivating voltage-gated ion channels that play a fundamental role in regulating neuronal excitability throughout the central and peripheral nervous systems [1, 5]. They are primarily composed of heterotetramers of KCNQ2 and KCNQ3 subunits (also known as Kv7.2 and Kv7.3), although KCNQ4 and KCNQ5 can also contribute to the M-current [3, 10]. These channels are unique for being open at subthreshold membrane potentials, where they provide a stabilizing outward potassium current that acts as a "brake" on repetitive action potential firing and prevents hyperexcitability [8, 12]. The activity of M-channels is tightly regulated by various signaling molecules, most notably phosphatidylinositol 4,5-bisphosphate (PIP2) and muscarinic acetylcholine receptors, the latter of which inhibit the channel to increase neuronal responsiveness [4, 12]. Dysfunction or mutations in the genes encoding these subunits are directly linked to several forms of epilepsy, including benign familial neonatal convulsions (BFNC) [3, 9]. Consequently, M-type channels are significant therapeutic targets; pharmacological activators like retigabine have been developed to treat seizures and are being investigated for conditions such as chronic pain and tinnitus [6, 7, 10].

Other names

M-currentKv7 channelKCNQ channelNeuronal M-channelKCNQ2/3 channelKv7.2/7.3 channel

Positive allosteric modulation of KCNQ2-5 subunits to increase channel open probability and hyperpolarize the membrane potential; or inhibition via pore blockade or muscarinic receptor-mediated depletion of PIP2.