STIMULATORY ACTION OF ANGIOTENSINII ON I_(KS) POTASSIUM CURRENT IN GUINEA-PIG ATRIAL CELLS

摘要

Present study aimed to investigate the effect of angiotensin II (AT H) on the slowly activating delayed rectifier K current (I_(Ks)) in guinea-pig atrial myocytes, search for responsible intracellular pathway(s), and record action potential during AT1-receptor activation using whole-cell patch-clamp technique. Bath-administration of AT II increased I_(KS) amplitude with Kh 6.16 nM, which was significantly prevented by valsartan (1 muM) and mimicked by the specific ATragonist Sar-AT II. In cells loaded with GDPpS (2 mM) or compound 48/80 (100 muM) as well as pretreatment with the protein kinase C (PKC) inhibitors H-7 (10 muM) or BIS (200 nM) abolished I_(Ks) potentiation extensively but it was not affected by intracellular perfusion of BAPTA (20 mM). No further enhancement of I_(KS) was measured after applying PKC-activator (PMA, 100 - 300 nM). Sar-AT II (100 nM) shortened action potential duration (APD) at 50 and 90% of repolarization by 50.4+-2.7% and 44.5+-2.0%, respectively. Subsequently added valsartan (1 muM) partially reversed APD. It is concluded that AT H enhances I_(KS) through activation of AT1-receptor coupled to G protein-PLC-PKC pathway and affects APD.