The inhibitory effect of Ca 2+-activated K + channel activator, BMS on L-type Ca 2+ channels in rat ventricular myocytes

Abstract

Aims We investigated the effects of BMS-204352 (BMS), a big-conductance calcium-activated potassium (BK Ca) channel activator, on L-type Ca 2+ channels. Main methods Electrophysiological recordings were performed in isolated rat ventricular myocytes. Whole-cell configuration was used. Key findings BMS caused inhibition of the Ca 2+ current in a dose-dependent manner, with K d of 6.00 ± 0.67 μM and a Hill coefficient of 1.33 ± 0.18. BMS did not affect the steady-state activation of L-type Ca 2+ channels. However, for those in steady-state inactivation, BMS shifted the half-maximal potential ( V 1/2) by − 11 mV, but the slope value ( k) was not altered. Iberiotoxin, inhibitor of membrane BK Ca channels and paxilline, inhibitor of mitochondrial BK Ca channel did not affect the inhibitory effect of BMS on L-type Ca 2+ channels. Pretreatment with inhibitors of protein kinase A (PKA), protein kinase C (PKC), and protein kinase G (PKG) did not significantly alter the inhibitory effect of BMS on L-type Ca 2+ current. The presence of a selective β-adrenergic receptor agonist, isoproterenol did not affect the inhibitory effect of BMS on L-type Ca 2+ current. Based on these results, we concluded that the inhibition of L-type Ca 2+ channels by BMS is independent of the inhibition of BK Ca channels or intracellular signaling pathways. Significance It is important to take BMS-204352 (BMS) effects on L-type Ca 2+ channels into consideration when using BMS as a BK Ca channel activator or therapeutic target in ventricular myocytes.