AJP - Heart and Circulatory Physiology, Vol 258, Issue 6 1796-H1805, Copyright © 1990 by American Physiological Society

ARTICLES

Mechanisms underlying early and delayed afterdepolarizations induced by catecholamines

S. G. Priori and P. B. Corr
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.

The relative influence of alpha- and beta-adrenergic receptor activation in eliciting early (EADs) and delayed (DADs) after depolarizations was assessed using intracellular microelectrode recordings in isolated adult canine ventricular myocytes. Normoxic myocytes were exposed to the alpha-adrenergic agonist phenylephrine (10(-8)-10(-6) M) or the beta-adrenergic agonist isoproterenol (10(-9)-10(-6) M) during pacing at different frequencies (0.5-4 Hz). alpha-Adrenergic stimulation resulted in a dose-dependent prolongation of action potential duration but failed to induce either EADs or DADs. beta-Adrenergic stimulation with isoproterenol at low concentrations (10(-9)-10(-8) M) induced a prolongation of the action potential, whereas higher concentrations (10(-7) and 10(-6) M) resulted in a marked shortening. Isoproterenol elicited single or multiple (2-5) DADs at concentrations from 10(-8) to 10(-6) M, with a corresponding increase in the amplitude of the DADs and decrease in the coupling interval as cells were paced at increasing rates. DADs often initiated and maintained sustained triggered rhythms that spontaneously terminated. Isoproterenol (10(-8)-10(-6) M) also elicited EADs in 80% of cells at the highest concentration utilized (10(-6) M) and at intermediate pacing frequencies (1-2 Hz). EADs often occurred with a 2:1 or 3:1 pattern. EADs and DADs induced by isoproterenol were reversibly abolished by low extracellular sodium, ryanodine (10(-6) M), or benzamil (10(-4) M), thus indicating that Ca2+ release from the sarcoplasmic reticulum and extracellular Na+ concentration are two major factors in the development of both types of afterdepolarizations. The demonstration that EADs can be induced by isoproterenol in ventricular muscle suggest a novel pathway for beta-adrenergic receptors to mediate arrhythmogenesis in the intact heart.

This article has been cited by other articles:

				K. Fujiwara, H. Tanaka, H. Mani, T. Nakagami, and T. Takamatsu Burst Emergence of Intracellular Ca2+ Waves Evokes Arrhythmogenic Oscillatory Depolarization via the Na+-Ca2+ Exchanger: Simultaneous Confocal Recording of Membrane Potential and Intracellular Ca2+ in the Heart Circ. Res., August 29, 2008; 103(5): 509 - 518. [Abstract] [Full Text] [PDF]

				G. Smith Matters of the heart: the physiology of cardiac function and failure Exp Physiol, November 1, 2007; 92(6): 973 - 986. [Abstract] [Full Text] [PDF]

				R. B. Huffaker, J. N. Weiss, and B. Kogan Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3089 - H3102. [Abstract] [Full Text] [PDF]

				D. Stilli, L. Bocchi, R. Berni, M. Zaniboni, F. Cacciani, C. Chaponnier, E. Musso, G. Gabbiani, and S. Clement Correlation of {alpha}-skeletal actin expression, ventricular fibrosis and heart function with the degree of pressure overload cardiac hypertrophy in rats Exp Physiol, May 1, 2006; 91(3): 571 - 580. [Abstract] [Full Text] [PDF]

				C. I. Spencer and J. S. K. Sham Effects of Na+/Ca2+ exchange induced by SR Ca2+ release on action potentials and afterdepolarizations in guinea pig ventricular myocytes Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2552 - H2562. [Abstract] [Full Text] [PDF]

				R. I.P. Dornan Anesthesia for a Patient with Catecholaminergic Polymorphic Ventricular Tachycardia Anesth. Analg., September 1, 2002; 95(3): 555 - 557. [Abstract] [Full Text] [PDF]

				Y. Song, J. C. Shryock, H. J. Knot, and L. Belardinelli Selective attenuation by adenosine of arrhythmogenic action of isoproterenol on ventricular myocytes Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2789 - H2795. [Abstract] [Full Text] [PDF]

				M. E. O'Leary Inhibition of Human Ether-A-Go-Go Potassium Channels by Cocaine Mol. Pharmacol., February 1, 2001; 59(2): 269 - 277. [Abstract] [Full Text]

				S. G. Priori, C. Napolitano, N. Tiso, M. Memmi, G. Vignati, R. Bloise, V. Sorrentino, and G. A. Danieli Mutations in the Cardiac Ryanodine Receptor Gene (hRyR2) Underlie Catecholaminergic Polymorphic Ventricular Tachycardia Circulation, January 16, 2001; 103(2): 196 - 200. [Abstract] [Full Text] [PDF]

				S. Viskin, R. Fish, A. Roth, P. J. Schwartz, and B. Belhassen QT or Not QT? N. Engl. J. Med., August 3, 2000; 343(5): 352 - 356. [Full Text] [PDF]

				D. J. Huelsing, K. W. Spitzer, and A. E. Pollard Electrotonic suppression of early afterdepolarizations in isolated rabbit Purkinje myocytes Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H250 - H259. [Abstract] [Full Text] [PDF]

				A. Mazur, D. M. Roden, and M. E. Anderson Systemic Administration of Calmodulin Antagonist W-7 or Protein Kinase A Inhibitor H-8 Prevents Torsade de Pointes in Rabbits Circulation, December 14, 1999; 100(24): 2437 - 2442. [Abstract] [Full Text] [PDF]

				E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]

				Y. Wu, D. M. Roden, and M. E. Anderson Calmodulin Kinase Inhibition Prevents Development of the Arrhythmogenic Transient Inward Current Circ. Res., April 30, 1999; 84(8): 906 - 912. [Abstract] [Full Text] [PDF]

				M. E. Anderson, A. P. Braun, Y. Wu, T. Lu, Y. Wu, H. Schulman, and R. J. Sung KN-93, an Inhibitor of Multifunctional Ca++/Calmodulin-Dependent Protein Kinase, Decreases Early Afterdepolarizations in Rabbit Heart J. Pharmacol. Exp. Ther., December 1, 1998; 287(3): 996 - 1006. [Abstract] [Full Text]

				M. W. Dae, R. J. Lee, P. C. Ursell, M. C. Chin, C. A. Stillson, and N. S. Moise Heterogeneous Sympathetic Innervation in German Shepherd Dogs With Inherited Ventricular Arrhythmia and Sudden Cardiac Death Circulation, August 19, 1997; 96(4): 1337 - 1342. [Abstract] [Full Text]

				S. G. Priori, C. Napolitano, F. Cantu, A. M. Brown, and P. J. Schwartz Differential Response to Na+ Channel Blockade, ß-Adrenergic Stimulation, and Rapid Pacing in a Cellular Model Mimicking the SCN5A and HERG Defects Present in the Long-QT Syndrome Circ. Res., June 1, 1996; 78(6): 1009 - 1015. [Abstract] [Full Text]

				M. A. Laflamme and P. L. Becker Ca2+-Induced Current Oscillations in Rabbit Ventricular Myocytes Circ. Res., April 1, 1996; 78(4): 707 - 716. [Abstract] [Full Text]

				P. J. Schwartz, S. G. Priori, E. H. Locati, C. Napolitano, F. Cantu, J. A. Towbin, M. T. Keating, H. Hammoude, A. M. Brown, L.-S. K. Chen, et al. Long QT Syndrome Patients With Mutations of the SCN5A and HERG Genes Have Differential Responses to Na+ Channel Blockade and to Increases in Heart Rate : Implications for Gene-Specific Therapy Circulation, December 15, 1995; 92(12): 3381 - 3386. [Abstract] [Full Text]

				X. Han and G. R. Ferrier Contribution of Na+-Ca2+ Exchange to Stimulation of Transient Inward Current by Isoproterenol in Rabbit Cardiac Purkinje Fibers Circ. Res., April 1, 1995; 76(4): 664 - 674. [Abstract] [Full Text]