Calcium currents in post-infarction rat cardiac myocytes.
Zhang, Xue-Qian, Russell L. Moore, Douglas L. Tillotson, and Joseph Y.
Cheung.
Departments of Medicine, and Cellular and Molecular Physiology,
Milton S. Hershey Medical Center, The Pennsylvania State University,
Hershey, Pennsylvania 17033; Department of Kinesiology, University of
Colorado, Boulder, Colorado 80309; and Department of Physiology,
Boston University School of Medicine, Boston, Massachusetts 02188
APStracts 2:0264C, 1995.
Myocytes isolated from rat hearts that have suffered 35% myocardial
infarction (MI) 3 weeks prior have lower peak cytosolic Ca2+
([Ca2+]i) during contraction when compared to Sham myocytes: a
difference that is amplified by isoproterenol or high extracellular
Ca2+ ([Ca2+]o). To evaluate whether reduced [Ca2+]i in MI myocytes is
due to decreased Ca2+ entry, we measured [3H]-PN200-110 (DHP) binding
and whole cell Ca2+ current (ICa). DHP binding decreased in both
sarcolemmal vesicles and intact myocytes from 3-week MI hearts. In
contrast, ICa was not different between Sham and MI myocytes
incubated at 1.8mM [Ca2+]o. At 5.0mM [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[mu]M) significantly increased ICa in Sham but not in
MI myocytes. Forskolin (10[mu]M) and dibutyrl cAMP (5mM)
significantly increased ICa in MI myocytes, the magnitude of ICa
increase was similar to that observed in Sham myocytes. We conclude:
(i) decreased systolic [Ca2+]i in MI myocytes was not due to reduced
Ca2+ entry via L-type Ca2+ channel; (ii) 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; (iii) reduction in isoproterenol-induced [Ca2+]i
increase in MI myocytes was partly due to decreased ICa, resulting in
less Ca2+ release from sarcoplasmic reticulum; (iv) the adenylate
cyclase/protein kinase A signal transduction pathway functioned
normally in MI myocytes; and (v) decreased [beta]-adrenergic
responsiveness in MI myocytes was likely due to altered coupling by
G-proteins.
Received 7 March 1995; accepted in final form 13 June 1995
APS Manuscript Number C127-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.