KMUP-1 inhibits L-type Ca 2+ channels involved the protein kinase C in rat basilar artery myocytes

摘要

This study investigated whether KMUP-1, a xanthine-based derivative, inhibits L-type Ca 2+ currents (I Ca,L ) in rat basilar artery smooth muscle cells (RBASMCs). We used whole cell patch-clamp recording to monitor Ba 2+ currents (I Ba ) through L-type Ca 2+ channels (LTCCs). Under voltage–clamp conditions, holding at –40mV, KMUP-1 (1, 3, 10μM) inhibited I Ba in a concentration-dependent manner and its IC 50 value was 2.27±0.45μM. A high concentration of KMUP-1 (10μM) showed without modifying the I Ba current–voltage relationship. On the other hand, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 1?μM) increase I Ba was inhibited by KMUP-1. Pretreatment with the PKC inhibitor chelerythrine (5μM) intensified KMUP-1-inhibited I Ba . However, the Rho kinase inhibitor Y-27632 (30μM) failed to affect the I Ba inhibition by KMUP-1. In light of these results, we suggest that KMUP-1 inhibition of LTCCs in concentration- and voltage-dependent manners in RBASMCs may be due, at least in part, to its modulation of the PKC pathway.