W-7 inhibits voltage-dependent K channels independent of calmodulin activity in rabbit coronary arterial smooth muscle cells

초록

We investigated the effect of W-7, a calmodulin inhibitor, on voltage-dependent K+ (Kv) channels in freshly isolated coronary arterial smooth muscle cells using the whole-cell patch clamp technique. The amplitude of Ky currents was inhibited by W-7 in a concentration-dependent manner, with an IC50 value of 3.38 +/- 0.47 mu M and a Hill coefficient of 0.84 +/- 0.10. W-7 shifted the activation curve to a more positive potential but had no significant effect on the inactivation curve, which indicated that W-7 inhibited the Ky current in a closed state of the Kv channel. Another calmodulin inhibitor, W-13, had no significant effect on Ky currents and did not change the inhibitory effect of W-7 on Ky channels. From these results, we conclude that W-7 inhibited the Kv current in a dose-dependent manner, but this inhibition occurred independent of calmodulin activity and in a closed (inactivated) state of the Ky channels. (C) 2015 Elsevier B.V. All rights reserved.

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