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Effect of the KCNQ potassium channel opener retigabine on single KCNQ2/3 channels expressed in CHO cells.
L Tatulian, D A Brown
J. Physiol. (Lond.),
, 549, 57-63
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 microM retigabine. The mean maximal open probability (Po) for single KCNQ2/3 channels was 0.13 +/- 0.02, with a half-maximal Po potential (Vo) of -28.7 +/- 1.4 mV for control recordings. Retigabine increased mean maximal Po to 0.38 +/- 0.04 and produced a hyperpolarising shift of Vo to -40.1 +/- 3.4 mV. Single KCNQ2/3 channels have multiple voltage-dependent kinetic components in their activity (CL-OS-CM-OL-CS; C = closed, O = open, L = long, S = short, M = medium), giving short, medium and long closed times (tauCS, tauCM, tauCL) and short and long open times (tauOS and tauOL). In the presence of retigabine at 0 mV the combined duration and contributions of the longest closed time tauCL 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.