The Ca<SUP>2+</SUP> Channel Iinhibitor NNC 55-0396 Inhibits Voltage-Dependent K<SUP>+</SUP> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

초록

We demonstrated the inhibitory effect of NNC 55-0396, a T-type Ca2+ channel inhibitor, on voltage-dependent K+ (K-V) channels in freshly isolated rabbit coronary arterial smooth muscle cells. NNC 55-0396 decreased the amplitude of K-V currents in a concentration-dependent manner, with an IC50 of 0.080 mu M and a Hill coefficient of 0.76. NNC 55-0396 did not affect steady-state activation and inactivation curves, indicating that the compound does not affect the voltage sensitivity of K-V channel gating. Both the K-V currents and the inhibitory effect of NNC 55-0396 on K-V channels were not altered by depletion of extracellular Ca2+ or intracellular ATP, suggesting that the inhibitory effect of NNC 55-0396 is independent of Ca2+-channel activity and phosphorylation-dependent signaling cascades. From these results, we concluded that NNC 55-0396 dose-dependently inhibits K-V currents, independently of Ca2+-channel activity and intracellular signaling cascades.

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