抄録
Angiotensin II (Ang II) produces numerous short- and long-term effects on cardiac muscle under various pathophysiological conditions. There is, however, little information concerning the immediate electrophysiological effects of Ang II on the cardiac repolarization process. The present study was designed to investigate the effect of Ang II on the slowly activating component of delayed rectifier K+ current (IKs) in guinea-pig atrial cells using the whole-cell patch-clamp technique. Bath application of Ang II (>=1 μM) increased the amplitude of IKs, evoked by 2-s depolarizing steps applied from a holding potential of -50 mV. The stimulatory effect of Ang II was largely abolished by the presence of the AT1 receptor antagonist valsartan (1 μM) and was mimicked by the specific AT1 agonist Sar-Ang II. These results indicate that IKs was enhanced via AT1 receptor. The stimulatory effect of Ang II was significantly reduced in cells loaded with nonhydrolyzable GDP analogue GDPβS (1 mM) or the phospholipase C (PLC) blocker compound 48/80. In addition, potentiation of IKs by Ang II was markedly reduced by pretreatment of the cells with the protein kinase C (PKC) inhibitors H-7 (10 μM) and BIS (100 nM) but was not affected by intracellular perfusion of BAPTA (20 mM).Based on these experimental results it is concluded that Ang II potentiates IKs by stimulating AT1 receptor couple to G protein-PLC-PKC pathway. [Jpn J Physiol 54 Suppl:S126 (2004)]
