Overview
- Main, M.J. et al. (2000) Mol. Pharmacol. 58, 253.
Alomone Labs Retigabine dihydrochloride modulates KCNQ2/KCNQ3 voltage-gated K+ currents expressed in Xenopus oocytes.A. Time course of KCNQ2/KCNQ3 current enhancement by 10 and 100 µM Retigabine dihydrochloride (#R-101) as measured at -50 mV. Currents were elicited by application of voltage ramp from a holding potential of -100 mV to 0 mV (800 msec). B. Superimposed example traces of current responses before and during perfusion of 10 and 100 µM Retigabine dihydrochloride, as indicated.
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 (KV7, 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 KV7.2/3 cells5 as well as other channels in the following order: KV7.3 > KV7.2/3 > KV7.2 > KV7.46. Similar effects were seen with 10 µM retigabine in oocytes expressing the KV7.2/3 heteromeric channel7.
