title: Calcium currents in postinfarction rat cardiac myocytes.
abstract: Myocytes isolated from rat hearts that have suffered 35% myocardial infarction (MI) 3 wk prior have lower peak cytosolic Ca2+ concentration ([Ca2+]i) during contraction compared with Sham myocytes, a difference that is amplified by isoproterenol or high extracellular Ca2+ concentration ([Ca2+]o). To evaluate whether reduced [Ca2+]i in MI myocytes is due to decreased Ca2+ entry, we measured [3H]PN-200-110 [dihydropyridine (DHP)] binding and whole cell Ca2+ current (ICa). DHP binding decreased in both sarcolemmal vesicles and intact myocytes from hearts 3 wk after MI. In contrast, ICa was not different between Sham and MI myocytes incubated at 1.8 mM [Ca2+]o. At 5.0 mM [Ca2+]o, ICa 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 microM) significantly increased ICa in Sham but not in MI myocytes. Forskolin (10 microM) dibutyryl adenosine 3',5'-cyclic monophosphate (5 mM) significantly increased ICa in MI myocytes; the magnitude of ICa increase was similar to that observed in Sham myocytes. We conclude that 1) decreased systolic [Ca2+]i in MI myocytes was not due to reduced Ca2+ entry via L-type Ca2+ channels; 2) discrepancy between DHP binding (decrease) and ICa (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 [Ca2+]i increase in MI myocytes was partly due to decreased ICa, resulting in less Ca2+ 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.
authors.affiliation: Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
authors.forename: X Q
authors.initials: XQ
authors.lastname: Zhang
authors.forename: R L
authors.initials: RL
authors.lastname: Moore
authors.forename: D L
authors.initials: DL
authors.lastname: Tillotson
authors.forename: J Y
authors.initials: JY
authors.lastname: Cheung
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D004095:Dihydropyridines / Q000378:metabolism; D004553:Electric Conductivity; D006321:Heart / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D017275:Isradipine / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism
chemical_list: D004095:Dihydropyridines; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D002118:Calcium; D017275:Isradipine