The Ca²⁺ Channel Iinhibitor NNC 55-0396 Inhibits Voltage-Dependent K⁺ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Abstract

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 μM 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 dosedependently inhibits K_V currents, independently of Ca²⁺-channel activity and intracellular signaling cascades.