Dyssynchronous Ca2+ Sparks in Myocytes From Infarcted Hearts

S. E. Litwin, D. Zhang, J. H. B. Bridge
2000 Circulation Research  
The kinetics of contractions and Ca 2ϩ 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 Ca 2ϩ transients during field stimulation in left ventricular (LV) myocytes from control and infarcted hearts (3 weeks). Compared with controls, Ca 2ϩ transients in myocytes adjacent to the
more » ... rct had lower peak amplitudes and prolonged time courses. Control myocytes showed relatively uniform changes in [Ca 2ϩ ] throughout the cell after electrical stimulation. In contrast, in MI myocytes [Ca 2ϩ ] increased inhomogeneously and localized increases in [Ca 2ϩ ] occurred throughout the rising and falling phases of the Ca 2ϩ transient. Ca 2ϩ content of the sarcoplasmic reticulum did not differ between MI and control myocytes. Peak L-type Ca 2ϩ 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 Ca 2ϩ transient/peak I Ca . However, when calculated as the peak rate of rise of the Ca 2ϩ transient/peak I Ca , the gain function was modestly decreased in the MI myocytes. Application of isoproterenol (100 nmol/L) improved the synchronization of Ca 2ϩ release in MI myocytes at both 0.5 and 1 Hz. The poorly coordinated production of Ca 2ϩ sparks in myocytes from infarcted rabbit hearts likely contributes to the diminished and slowed macroscopic Ca 2ϩ transient. These abnormalities can be largely overcome when phosphorylation of Ca 2ϩ cycling proteins is enhanced by ␤-adrenergic stimulation.
doi:10.1161/01.res.87.11.1040 pmid:11090550 fatcat:qlik52p65vgmhbgj5mwiioawre