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

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  • Yazawa Kazuto
    Department of Pharmacology, Akita University School of Medicine
  • Ono Kyoichi
    Department of Pharmacology, Akita University School of Medicine
  • Iijima Toshihiko
    Department of Pharmacology, Akita University School of Medicine

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  • Modulation by Mibefradil of the Histamine-Induced Ca〔2+〕 Entry in Human Aortic Endothelial Cells

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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.<br>

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