Modulation by Mibefradil of the Histamine-Induced Ca²⁺ Entry in Human Aortic Endothelial Cells

Abstract

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.