Sarcolemmal Ca2+-ATPase ability to transport Ca2+ gradually diminishes after myocardial infarction in the rat

Abstract

Aims: Plasmalemmal Ca2+-ATPase (PMCA) is involved in Ca 2+ handling and the regulation of intracellular signalling pathways in the heart. However, there is no information on its functioning in heart hypertrophy and failure. We aimed to investigate the Ca2+- transporting ability of PMCA, Na+/Ca2+ exchanger (NCX), and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), as well as the amplitude of Ca2+ transients and cell shortening in myocytes isolated from rat hearts at various time intervals after myocardial infarction (MI). Methods and results: The rate of Ca2+ transport by PMCA, NCX, and SERCA2a was estimated from the rate constants of decay of electrically and caffeine-evoked Ca2+ transients in left ventricular myocytes isolated 1 week, 1 month, and 3 months after MI. One week, 1 month, and 3 months after MI, the transporting function of PMCA decreased by 27, 41, and 67%, respectively, compared with that in time-matched sham animals. This was accompanied by increased amplitude of Ca2+ transients, cell shortening, and SR Ca2+ content. Carboxyeosin, a blocker of PMCA, increased the amplitude of shortening in cells extracted from control hearts. This effect was absent 1 and 3 months after MI. PMCA1, 2, and 4 mRNAs were unchanged in the ventricular muscle 3 months after MI when compared with time-matched sham animals. The transporting function of NCX was increased by 65% only 3 months after MI, whereas that of SERCA2a was decreased by ∼18% at all three time points after MI. Conclusion: The ability of PMCA to transport Ca2+ progressively decreases over 3 months after MI. This decrease may contribute to the increase in amplitude of Ca2+ transients and myocyte shortening. © The Author 2008.