Effect of the KCNQ potassium channel opener retigabine on single KCNQ2/3 channels expressed in CHO cells |
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Authors: | L Tatulian D A Brown |
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Institution: | Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK |
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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 (CL-OS-CM-OL-CS; C = closed, O = open, L = long, S = short, M = medium), giving short, medium and long closed times (τCS, τCM, τCL) and short and long open times (τOS and τOL). In the presence of retigabine at 0 mV the combined duration and contributions of the longest closed time τCL 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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