This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zankov, D. P. Articles by Horie, M. Search for Related Content PubMed PubMed Citation Articles by Zankov, D. P. Articles by Horie, M. Related Collections Cardiovascular Pharmacology ACE/Angiotension receptors Arrythmias-basic studies Ion channels/membrane transport Arrhythmias, clinical electrophysiology, drugs

(Circulation. 2006;113:1278-1286.)
© 2006 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Angiotensin II Potentiates the Slow Component of Delayed Rectifier K⁺ Current via the AT₁ Receptor in Guinea Pig Atrial Myocytes

Dimitar P. Zankov, MD; Mariko Omatsu-Kanbe, PhD; Takahiro Isono, PhD; Futoshi Toyoda, PhD; Wei-Guang Ding, MD, PhD; Hiroshi Matsuura, MD, PhD; Minoru Horie, MD, PhD

From the Departments of Physiology (D.P.Z., M.O.-K., F.T., W.-G.D., H.M.) and Cardiovascular and Respiratory Medicine (D.P.Z., M.H.) and the Central Research Laboratory (T.I.), Shiga University of Medical Science, Otsu, Shiga, Japan.

Correspondence to Minoru Horie, MD, PhD, Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan. E-mail horie{at}belle.shiga-med.ac.jp

Received December 18, 2004; revision received January 10, 2006; accepted January 11, 2006.

Background— 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.

Methods and Results— The present study investigated the immediate effects of Ang II on the slow component of delayed rectifier K⁺ current (I_Ks) and action potentials in guinea pig atrial myocytes using the whole-cell patch-clamp technique. Bath application of Ang II increased the amplitude of I_Ks (EC₅₀, 6.16 nmol/L) concentration dependently. The stable analogue Sar¹–Ang II was also effective at increasing I_Ks. The voltage dependence of I_Ks activation and the kinetics of deactivation were not significantly affected by these agonists. The enhancement of I_Ks was blocked by the Ang II type 1 (AT₁) receptor antagonist valsartan (1 µmol/L) and was markedly attenuated by inclusion of GDPßS (2 mmol/L) in the pipette, indicating an involvement of G protein–coupled AT₁ receptor. The stimulatory effect was also significantly reduced by the phospholipase C inhibitor compound 48/80 (100 µmol/L) and the protein kinase C inhibitors bisindolylmaleimide I (200 nmol/L) and H-7 (10 µmol/L), suggesting that AT₁ receptor acts through phospholipase C–protein kinase C signaling cascade to potentiate I_Ks. As expected from its stimulatory action on I_Ks, Sar¹–Ang II markedly shortened the action potential duration, which could be reversed by valsartan.

Conclusions— The potentiation of I_Ks via AT₁ stimulation in atrial myocytes, accompanied by a shortening of the action potential duration, suggests a potential mechanism by which elevated levels of Ang II may promote atrial fibrillation in heart failure and warrants further investigation.

---

 

CLINICAL PERSPECTIVE

This article has been cited by other articles:

				A. Bollmann, A. Tveit, D. Husser, M. Stridh, L. Sornmo, P. Smith, and S. B. Olsson Fibrillatory rate response to candesartan in persistent atrial fibrillation Europace, October 1, 2008; 10(10): 1138 - 1144. [Abstract] [Full Text] [PDF]

				R. Laszlo, C. Eick, N. Rueb, S. Weretka, H.-J. Weig, J. Schreieck, and R. F Bosch Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium Journal of Renin-Angiotensin-Aldosterone System, September 1, 2008; 9(3): 125 - 132. [Abstract] [PDF]

				A. Goette and U. Lendeckel Electrophysiological effects of angiotensin II. Part I: signal transduction and basic electrophysiological mechanisms Europace, February 1, 2008; 10(2): 238 - 241. [Abstract] [Full Text] [PDF]

				R. Due-Andersen, T. Hoi-Hansen, N. V. Olsen, C. E. Larroude, J. K. Kanters, F. Boomsma, U. Pedersen-Bjergaard, and B. Thorsteinsson Cardiac repolarization during hypoglycaemia and hypoxaemia in healthy males: impact of renin-angiotensin system activity Europace, February 1, 2008; 10(2): 219 - 226. [Abstract] [Full Text] [PDF]

				T. Christ, E. Wettwer, and U. Ravens Letter by Christ et al Regarding Article, "Angiotensin II Potentiates the Slow Component of Delayed Rectifier K+ Current via the AT1 Receptor in Guinea Pig Atrial Myocytes" Circulation, October 31, 2006; 114(18): e565 - e565. [Full Text] [PDF]

				D. P. Zankov, M. Omatsu-Kanbe, F. Toyoda, W.-G. Ding, H. Matsuura, T. Isono, and M. Horie Response to Letter Regarding Article, "Angiotensin II Potentiates the Slow Component of Delayed Rectifier K+ Current via the AT1 Receptor in Guinea Pig Atrial Myocytes" Circulation, October 31, 2006; 114(18): e566 - e566. [Full Text] [PDF]