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 Ca 2+ 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 KV 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 KV channel gating. Both the KV currents and the inhibitory effect of NNC-55-0396 on KV channels were not altered by depletion of extracellular Ca2+ or intracellular ATP, suggesting that the inhibitory effect of NNC-55-0396 is independent of Ca 2+-channel activity and phosphorylation-dependent signaling cascades. From these results, we concluded that NNC-55-0396 dose-dependently inhibits KV currents, independently of Ca2+-channel activity and intracellular signaling cascades. © The Japanese Pharmacological Society.