Potassium voltage-gated channel subfamily KQT member 2, 3, 4, and 5 (Kv7.2-7.5)

The Kv7.2-7.5 voltage-gated potassium channels, encoded by the KCNQ2, KCNQ3, KCNQ4, and KCNQ5 genes, are critical regulators of neuronal excitability in the central and peripheral nervous systems [1, 3]. These channels are the primary molecular components of the M-current, a slow, non-inactivating potassium current that activates at subthreshold membrane potentials to stabilize the resting membrane potential and control repetitive firing [4, 5]. Mutations in these channels are associated with a spectrum of neurological disorders, including benign familial neonatal convulsions, severe developmental and epileptic encephalopathy, and certain forms of inherited deafness [2, 9]. Pharmacological activation of Kv7.2-7.5 channels, particularly the Kv7.2/7.3 heteromers, serves as a potent therapeutic strategy for treating epilepsy and neuropathic pain by dampening neuronal hyperexcitability [6, 13]. Drugs like retigabine (ezogabine) act as positive allosteric modulators by shifting the voltage-dependence of channel activation to more hyperpolarized potentials [8, 12]. However, therapeutic development has been complicated by safety concerns such as urinary retention and tissue pigmentation, driving the search for more selective next-generation modulators [12, 14].

Other names

KCNQ2KCNQ3KCNQ4KCNQ5Neuronal Kv7 channelsM-channel

Positive allosteric modulation (activators) and pore blockade (inhibitors)