Open AccessKMUP‐1 inhibits L‐type Ca 2+ channels involved the protein kinase C in rat basilar artery myocytes
Author(s) -
Chen JunYih,
Jiang MinChi,
Chu LiWen,
Hsieh SuLing,
Chen IngJun,
Wu BinNan
Publication year - 2011
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2011.10.026
Subject(s) - chelerythrine , protein kinase c , patch clamp , activator (genetics) , phorbol , biophysics , medicine , kinase , biochemistry , biology , electrophysiology , receptor
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 –40 mV, KMUP‐1 (1, 3, 10 μM) inhibited I Ba in a concentration‐dependent manner and its IC 50 value was 2.27 ± 0.45 μM. A high concentration of KMUP‐1 (10 μM) 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 (5 μM) intensified KMUP‐1‐inhibited I Ba . However, the Rho kinase inhibitor Y‐27632 (30 μM) 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.