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

L. Tatulian and D. A. Brown

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 µM 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 (_CS, _CM, _CL) and short and long open times (_OS and _OL). In the presence of retigabine at 0 mV the combined duration and contributions of the longest closed time _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.

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