Calcium currents in postinfarction rat cardiac myocytes
Zhang, X.Q.; Moore, R.L.; Tillotson, D.L.; Cheung, J.Y.
American Journal of Physiology 269(6 Pt 1): C1464-C1473
1995
ISSN/ISBN: 0002-9513 PMID: 8572175 Document Number: 443645
Myocytes isolated from rat hearts that have suffered 35% myocardial infarction (MI) 3 wk prior have lower peak cytosolic Ca-2+ concentration ((Ca-2+)-i) during contraction compared with Sham myocytes, a difference that is amplified by isoproterenol or high extracellular Ca-2+ concentration ((Ca-2+)-o). To evaluate whether reduced (Ca-2+)-i in MI myocytes is due to decreased Ca-2+ entry, we measured (3H)PN200-110 (dihydropyridine (DHP)) binding and whole cell Ca-2+ current (I-Ca). DHP binding decreased in both sarcolemmal vesicles and intact myocytes from hearts 3 wk after MI. In contrast, I-Ca was not different between Sham and MI myocytes incubated at 1.8 mM (Ca-2+)-o. At 5.0 mM (Ca-2+)-o, I-Ca increased similarly in Sham and MI myocytes. Steady-state voltage dependence of activation and inactivation were similar between Sham and MI myocytes, as were the fast- and slow inactivation time constants. Isoproterenol (1 mu-M) significantly increased I-Ca in Sham but not in MI myocytes. Forskolin (10 mu-M) and dibutyryl adenosine 3',5'-cyclic monophosphate (5 mM) significantly increased I-Ca in MI myocytes; the magnitude of I-Ca increase was similar to that observed in Sham myocytes. We conclude that 1) decreased systolic (Ca-2+)-i in MI myocytes was not due to reduced Ca-2+ entry via L-type Ca-2+ channels; 2) discrepancy between DHP binding (decrease) and I-Ca (no change) results may be explained by higher channel availability and/or increased long-opening modes (mode 2) in MI myocytes; 3) reduction in isoproterenol-induced (Ca-2+)-i increase in MI myocytes was partly due to decreased I-Ca, resulting in less Ca-2+ release from sarcoplasmic reticulum; 4) the adenylate cyclase-protein kinase A signal-transduction pathway functioned normally in MI myocytes; and 5) decreased beta-adrenergic responsiveness in MI myocytes was likely due to altered coupling by G proteins.