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 Ca2+ channel antagonist, on the histamine-induced Cl- current and Ca2+ entry was investigated in human aortic endothelial cells by the fluorescence measurement of intracellular Ca2+ concentration ([Ca2+]i) combined with the patch clamp method. Mibefradil (10 μM) inhibited both the Cl- current and Ca2+ entry in a concentration-dependent manner with an IC50 value of 4.8 and 2.6 μM for the Cl- current and [Ca2+]i, respectively. These values were comparable to those reported for the inhibition of the T-type Ca2+ channel and other Cl- channels. The suppression of Ca2+ 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 Ca2+ entry channels in vascular endothelial cells.