Effect of ablation of phospholamban on dynamics of cardiac myocyte
contraction and intracellular calcium under basal conditions and
during [beta]-adreneric stimulation.
Wolska, Beata M., Miroslav O. Stojanovic, Weisheng Luo, Evangelia G.
Kranias, and R. John Solaro.
Department of Physiology and Biophysics, University of Illinois at
Chicago, College of Medicine, Chicago, IL 60612 and Department of
Pharmacology and Cell Biophysics, University of Cincinnati, College
of Medicine, Cincinnati, OH 45267
APStracts 3:0056C, 1996.
We compared mechanical activity and Ca2+ transients of ventricular
myocytes isolated from wild-type and phospholamban (PLB)-deficient
mouse hearts in control conditions and during [beta]-adrenergic
stimulation. Compared to wild-type controls, cells isolated from PLB
-deficient mouse hearts showed: i) a 2-fold increase in extent of cell
shortening, ii) a 3-fold increase in maximal shortening velocity, and
iii) a 3.4-fold increase in maximal relengthening velocity. PLB
-deficient myocytes also demonstrated significant increases in the
peak amplitude of the fura-2 fluorescence ratio and the rates of
rising and falling phases of the Ca2+ transient. The fura-2 diastolic
ratios were similar in both groups, suggesting no change in Cai2+
during diastole. In PLB-deficient myocytes, 0.05 [mu]M isoproterenol
induced an increase in the twitch amplitude by 152 +/- 11 % (n=6)
compared to 290 +/- 31 % (n=6) in wild-type cells. Maximal shortening
velocity was increased by 183 +/- 10 % (n=6) in PLB-deficient
myocytes, compared to 398 +/- 62 % (n=6) in wild-type cells. The
isoproterenol induced increase in maximum relengthening velocity was
increased by 168 +/- 8 % (n=6) in PLB-deficient cells compared to 445
+/- 71 % (n=6) in wild-type myocytes. In both groups these changes in
contractile parameters were accompanied by changes in the Ca2+
transient. Our results indicate that phosphorylation of sites other
than PLB may play an important role in regulation of
contraction/relaxation dynamics of heart cells responding to [beta]
-adrenergic stimulation.
Received 20 October 1995; accepted in final form 5 February 1996.
APS Manuscript Number C639-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96