Heteromeric KCNQ5/Q3 channels were stably expressed in Chinese Hamster ovary cells and characterized using the whole cell voltage‐clamp technique. KCNQ5/Q3 channels were activated by the novel anticonvulsant, retigabine (EC₅₀ 1.4 μM) by a mechanism that involved drug‐induced, leftward shifts in the voltage‐dependence of channel activation (−31.8 mV by 30 μM retigabine). KCNQ5/Q3 channels were inhibited by linopirdine (IC₅₀ 7.7 μM) and barium (IC₅₀ 0.46 mM), at concentrations similar to those required to inhibit native M‐currents. These findings identify KCNQ5/Q3 channels as a molecular target for retigabine and raise the possibility that activation of KCNQ5/Q3 channels may be responsible for some of the anti‐convulsant activity of this agent. Furthermore, the sensitivity of KCNQ5/Q3 channels to linopirdine supports the possibility that potassium channels comprised of KCNQ5 and KCNQ3 may make a contribution to native M‐currents.

British Journal of Pharmacology (2001) 132, 381–384; doi:10.1038/sj.bjp.0703861