Potassium channel subunit Kv7.2–Kv7.5 (Kv7.2–Kv7.5)

Kv7.2–Kv7.5 potassium channels are tetrameric, voltage-gated ion channels composed of α subunits with six transmembrane segments (S1–S6) each, forming voltage-sensing and pore domains. These channels control neuronal excitability by mediating the M-current—a slowly activating, non-inactivating potassium current that stabilizes cell membrane potential. They are crucial for normal brain function, muscle contractility, and cardiac rhythm. Disease mutations or pharmacological modulation of these channels can cause or treat epilepsy, arrhythmias, and abnormal smooth muscle contraction. They are highly sensitive to the lipid PIP2 and are regulated via various signaling cascades, including Gq-coupled receptor pathways. Retigabine and flupirtine were clinically used as channel activators for epilepsy and pain but are no longer marketed due to safety issues.

Other names

KCNQ2–KCNQ5 channelsVoltage-gated potassium channel subunit KCNQ2/KCNQ3/KCNQ4/KCNQ5M-channels

Positive modulation (activation) of M-current (shifting voltage-dependence and promoting opening of channels, e.g., by retigabine/flupirtine); Inhibition/modulation via receptor-mediated PIP2 depletion (e.g., muscarinic receptor inhibition of M-current)