© 2000 American Heart Association, Inc.
Cellular Biology |
Dyssynchronous Ca2+ Sparks in Myocytes From Infarcted Hearts
Presented in part at the American Heart Association meeting, Cellular and Molecular Mechanisms of Heart Failure, Snowbird, Utah, August 18–22, 1999, and the Biophysical Society Meeting, New Orleans, La, February 12–16, 2000, and published in abstract form (Biophys J. 2000;78:439A).
From the Division of Cardiology, Veterans Affairs Medical Center (S.E.L., D.Z.), the Division of Cardiology, University of Utah (S.E.L., J.H.B.B.), and the Nora Eccles Harrison Cardiovascular and Research Training Institute (J.H.B.B.), Salt Lake City, Utah.
Correspondence to Sheldon E. Litwin, MD, Cardiovascular Division, University of Utah Hospital, 50 N Medical Dr, Salt Lake City, UT 84132. E-mail sheldon.litwin{at}hsc.utah.edu
Abstract—The kinetics of contractions and Ca2+ transients are slowed in myocytes from failing hearts. The mechanisms accounting for these abnormalities remain unclear. Myocardial infarction (MI) was produced by ligation of the circumflex artery in rabbits. We used confocal microscopy to record spatially resolved Ca2+ transients during field stimulation in left ventricular (LV) myocytes from control and infarcted hearts (3 weeks). Compared with controls, Ca2+ transients in myocytes adjacent to the infarct had lower peak amplitudes and prolonged time courses. Control myocytes showed relatively uniform changes in [Ca2+] throughout the cell after electrical stimulation. In contrast, in MI myocytes [Ca2+] increased inhomogeneously and localized increases in [Ca2+] occurred throughout the rising and falling phases of the Ca2+ transient. Ca2+ content of the sarcoplasmic reticulum did not differ between MI and control myocytes. Peak L-type Ca2+ current density was reduced in MI myocytes. The macroscopic gain function was not different in control and MI myocytes when calculated as the amplitude of the Ca2+ transient/peak ICa. However, when calculated as the peak rate of rise of the Ca2+ transient/peak ICa, the gain function was modestly decreased in the MI myocytes. Application of isoproterenol (100 nmol/L) improved the synchronization of Ca2+ release in MI myocytes at both 0.5 and 1 Hz. The poorly coordinated production of Ca2+ sparks in myocytes from infarcted rabbit hearts likely contributes to the diminished and slowed macroscopic Ca2+ transient. These abnormalities can be largely overcome when phosphorylation of Ca2+ cycling proteins is enhanced by ß-adrenergic stimulation.
Key Words: myocardial infarction • calcium channels • heart failure • sarcoplasmic reticulum • sparks
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