The KCNQ family of voltage-gated K⁺ channels includes 5 known members: KCNQ1 to KCNQ5. Structurally, the KCNQ family belongs to the six transmembrane domain category of K⁺ channels. KCNQ family members can form either homomultimeric or heteromultimeric channels with different functional consequences. For example, KCNQ2 and KCNQ3 heteromultimers give rise to a much larger channel current than when either protein is expressed alone. Indeed, KCNQ2/KCNQ3 heteromultimers are believed to be the molecular correlates of the so-called M current. This current is a K⁺ neuronal current that is strongly inhibited by the activation of the M₁ subtype of the muscarinic acetylcholine receptor. Mutations in either KCNQ2 or KCNQ3 are associated with a form of epilepsy known as benign familial neonatal convulsions (BNFC)^1-3.

Retigabine is a potent and selective KCNQ (K_V7, M-) channel modulator (enhancer)^4-7, which is used in the clinic to treat epilepsy⁸. Retigabine (0.1 to 10 µM) induced a K⁺ current and hyperpolarized CHO cells expressing K_V7.2/3 cells⁵ as well as other channels in the following order: K_V7.3 > K_V7.2/3 > K_V7.2 > K_V7.4⁶. Similar effects were seen with 10 µM retigabine in oocytes expressing the K_V7.2/3 heteromeric channel⁷.