Potassium channel subfamily KQT member 2 and Potassium channel subfamily KQT member 3 (KCNQ2/KCNQ3)

KCNQ2/KCNQ3 potassium channels are neuronal voltage-gated ion channels that form heteromeric complexes mediating the M-type potassium current (M-current) in the central and peripheral nervous system. The channels are composed of four subunits, often a mixture of KCNQ2 and KCNQ3, and are essential in regulating neuronal excitability by stabilizing the resting membrane potential and limiting repetitive firing. They localize at axon initial segments and nodes of Ranvier, acting as gatekeepers for action potential initiation and propagation. Mutations cause benign familial neonatal convulsions and other epilepsy syndromes. Drugs such as retigabine selectively activate these channels, serving as treatments for seizure disorders. KCNQ2/KCNQ3 channel function is regulated by PIP2, protein interactions, phosphorylation, and calmodulin. Suppression or malfunction is linked to hyperexcitability and neurological disease, making them key targets for neurotherapeutics.

Other names

Kv7.2/Kv7.3KCNQ2/KCNQ3 heteromeric potassium channelsM-channelNeuronal M-current channelPotassium voltage-gated channel subfamily KQT member 2/3

Positive allosteric modulation/activation: Retigabine, ZnPy, and related compounds increase channel opening by hyperpolarizing the activation voltage and/or stabilizing the open state. Blockade/inhibition: XE991, linopirdine, and TEA block KCNQ2/KCNQ3 channels, reducing M-current and increasing neuronal excitability.