Effect of the KCNQ potassium channel opener retigabine on single KCNQ2/3 channels expressed in CHO cells

Abstract

KCNQ2/3 potassium channel subunits were co‐expressed in Chinese hamster ovary (CHO) cells and currents through single channels recorded using cell‐attached patches. Channels had a similar slope conductance in the presence (8.04 ± 0.02 pS) and absence (7.6 ± 0.01 pS) of 10 μ m retigabine. The mean maximal open probability ( P o ) for single KCNQ2/3 channels was 0.13 ± 0.02, with a half‐maximal P o potential ( V o ) of −28.7 ± 1.4 mV for control recordings. Retigabine increased mean maximal P o to 0.38 ± 0.04 and produced a hyperpolarising shift of V o to −40.1 ± 3.4 mV. Single KCNQ2/3 channels have multiple voltage‐dependent kinetic components in their activity (C L ‐O S ‐C M ‐O L ‐C S ; C = closed, O = open, L = long, S = short, M = medium), giving short, medium and long closed times (τ CS , τ CM , τ CL ) and short and long open times (τ OS and τ OL ). In the presence of retigabine at 0 mV the combined duration and contributions of the longest closed time τ CL decreased tenfold, while the short and long open times increased fourfold and twofold, respectively. Thus, steady‐state kinetics were modified to favour the open channel configuration.