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

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 muM retigabine. The mean maximal open probability (P(o)) for single KCNQ2/3 channels was 0.13 +/- 0.02, with a halfmaximal 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 (tau-(CS), tau(CM), tau(CL)) and short and long open times (tau(OS) and tau(OL)). In the presence of retigabine at 0 mV the combined duration and contributions of the longest closed time tau(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.