| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 93 === Labedipinedilol-A has been described to have ��/��-adrenoceptor and calcium channel blocking activities, and to inhibit the proliferation of vascular smooth muscle cells. However, a direct evidence of calcium currents inhibition by labedipinedilol-A has not yet been documented.
This study is to examine the effects of labedipinedilol-A on L-type calcium currents (ICa,L). We used the conventional whole cell patch-clamp technique to investigete Ba2+ currents (IBa) through L-type Ca2+ channels in rat cerebral artery myocytes. The IBa was reduced by nifedipine (1 �嵱) and enchanced by Bay K8644 (100 nM). Under voltage-clamp conditions, labedipinedilol-A (1 �嵱) reversibly inhibited the IBa in a concentration-dependent manner but without any change in current-voltage relationship of IBa. Additionally, labedipinedilol-A shifted the steady-state inactivation curve of IBa to more negative potentials. Labedipinedilol-A had a greater inhibitory activity holding at –40 mV than at -80 mV. This phenomenon of voltage-dependency by labedipinedilol-A might contribute to its higher potency in vascular smooth muscle. Pretreatment with the protein kinase C (PKC) inhibitor chelerythrine (5 �嵱) attenuated the inhibition of IBa by labedipinedilol-A. However, Rho kinase inhibitor Y-27632 (30 �嵱) failed to affect the inhibition of IBa by labedipinedilol-A. In light of these results, we suggest that labedipinedilol-A inhibits the L-type calcium channels in concentration- and voltage-dependent manners in rat cerebral artery myocytes and the effects may partially related to the PKC pathway.
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