Angiotensin II potentiates the slow component of delayed rectifier K+ current via the AT1 receptor in guinea pig atrial myocytes

Circulation
Dimitar P ZankovM Horie

Abstract

Angiotensin II (Ang II) has diverse actions on cardiac electrical activity. Little information is available, however, regarding immediate electrophysiological effects of Ang II on cardiac repolarization. The present study investigated the immediate effects of Ang II on the slow component of delayed rectifier K+ current (IKs) and action potentials in guinea pig atrial myocytes using the whole-cell patch-clamp technique. Bath application of Ang II increased the amplitude of IKs (EC50, 6.16 nmol/L) concentration dependently. The stable analogue Sar1-Ang II was also effective at increasing IKs. The voltage dependence of IKs activation and the kinetics of deactivation were not significantly affected by these agonists. The enhancement of IKs was blocked by the Ang II type 1 (AT1) receptor antagonist valsartan (1 micromol/L) and was markedly attenuated by inclusion of GDPbetaS (2 mmol/L) in the pipette, indicating an involvement of G protein-coupled AT(1) receptor. The stimulatory effect was also significantly reduced by the phospholipase C inhibitor compound 48/80 (100 micromol/L) and the protein kinase C inhibitors bisindolylmaleimide I (200 nmol/L) and H-7 (10 micromol/L), suggesting that AT1 receptor acts through phospholipase C-p...Continue Reading

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Citations

May 2, 2008·European Biophysics Journal : EBJ·Alison Gurney, Boris Manoury
May 1, 2009·Pflügers Archiv : European journal of physiology·Dimitar P ZankovMinoru Horie
Jul 31, 2008·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Andreas BollmannS Bertil Olsson
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