Modulation by mibefradil of the histamine-induced Ca2+ entry in human aortic endothelial cells

The effect of mibefradil, known as a T- and L-type Ca(2+) channel antagonist, on the histamine-induced Cl(-) current and Ca(2+) entry was investigated in human aortic endothelial cells by the fluorescence measurement of intracellular Ca(2+) concentration ([Ca(2+)](i)) combined with the patch clamp method. Mibefradil (10 micro M) inhibited both the Cl(-) current and Ca(2+) entry in a concentration-dependent manner with an IC(50) value of 4.8 and 2.6 micro M for the Cl(-) current and [Ca(2+)](i), respectively. These values were comparable to those reported for the inhibition of the T-type Ca(2+) channel and other Cl(-) channels. The suppression of Ca(2+) entry is not caused by the inhibition of the Cl(-) current and the resulting depolarization since the inhibition was still observed under the voltage clamp condition. These results suggest that mibefradil is a potent blocker not only for the agonist-induced Cl(-) current but also Ca(2+) entry channels in vascular endothelial cells.