Neuronal voltage-gated potassium channels Kv7.2–Kv7.5 (Kv7.2–Kv7.5)

Neuronal voltage-gated potassium channels Kv7.2–Kv7.5, encoded by the KCNQ2–5 genes, are essential regulators of electrical activity in the central and peripheral nervous systems [1, 2]. These channels assemble as homo- or heterotetramers to generate the M-current, a slow-activating, non-inactivating potassium current that serves as a physiological brake to prevent repetitive action potential firing and stabilize the resting membrane potential [4, 7]. Dysfunction of these channels due to genetic mutations is a primary cause of various hyperexcitability disorders, including benign familial neonatal seizures (BFNS), severe developmental and epileptic encephalopathy (DEE), and hereditary deafness [8, 10, 12]. Pharmacological activation of Kv7 channels has proven to be an effective therapeutic strategy for epilepsy and is being explored for neuropathic pain and tinnitus [11, 18]. While the first-in-class activator retigabine was successful in treating seizures, its clinical use was curtailed by off-target safety issues such as tissue pigmentation, leading to the current development of more selective, next-generation modulators like XEN1101 [15, 17].

Other names

KCNQ2KCNQ3KCNQ4KCNQ5M-channelPotassium voltage-gated channel subfamily KQT member 2Potassium voltage-gated channel subfamily KQT member 3Potassium voltage-gated channel subfamily KQT member 4Potassium voltage-gated channel subfamily KQT member 5KQT-like 2KQT-like 3KQT-like 4KQT-like 5

Positive allosteric modulation of voltage-gated potassium channels, primarily by shifting the voltage-dependence of activation to more hyperpolarized (negative) potentials, thereby increasing the probability of the channel being open at resting or subthreshold voltages.