Potassium voltage-gated channel subfamily Q members 2-5 (KCNQ2-5) (KCNQ2-5)

The KCNQ2-5 neuronal potassium channels, also known as the Kv7.2-7.5 channels, are a group of voltage-gated potassium channels primarily expressed in the central and peripheral nervous systems (UniProt: O43526, O43525). These channels are responsible for generating the M-current, a slow-activating and non-inactivating potassium current that plays a critical role in regulating neuronal excitability and determining the resting membrane potential (PubMed: 29345340). By controlling the threshold for action potential firing, KCNQ2-5 channels act as a 'brake' on repetitive neuronal activity (PubMed: 22405631). Dysregulation or mutations in the genes encoding these subunits are linked to various neurological disorders, most notably benign familial neonatal convulsions (BFNC) and developmental and epileptic encephalopathy (NIH: GeneReviews NBK1521). Pharmacological activation of these channels, particularly the KCNQ2/3 heteromer, has proven to be an effective strategy for treating epilepsy and is being explored for neuropathic pain and mood disorders (PubMed: 30115634). While the first-in-class opener retigabine was successful in reducing seizures, its clinical use was limited by off-target effects such as urinary retention and tissue discoloration (StatPearls: NBK545191). Modern drug development focuses on more selective KCNQ2/3 or KCNQ2/3/5 activators to improve safety profiles and therapeutic efficacy (PubMed: 34135156).

Other names

Kv7.2-7.5M-channelNeuronal Kv7 channelsKQT-like 2-5

Positive allosteric modulation of voltage-gated potassium channels, shifting the voltage-dependence of activation to more hyperpolarized potentials to stabilize the resting membrane potential and reduce neuronal hyperexcitability (PubMed: 21502326).