Cardiac myocyte volume, ca2+ fluxes and sarcoplasmic reticulum
loading in pressure overload hypertrophy.
Delbridge, Leanne M. D., Hiroshi Satoh, Weilong Yuan, Jose W. M.
Bassani, Ming Qi, Kenneth S. Ginsburg, Allen M. Samarel, and Donald
M. Bers.
Department of Physiology and Cardiovascular Institute, Loyola
University Chicago, Stritch School of Medicine, Maywood, IL 60153,
USA
APStracts 3:0497H, 1996.
Alterations in cellular Ca2+ transport and excitation-contraction
coupling may contribute to dysfunction in cardiac hypertrophy. Left
ventricular myocytes were isolated from rat hearts after 15-18 weeks
of supra-renal abdominal aortic banding to evaluate the hypothesis
that hypertrophy alters the relationship between Ca2+ current (ICa)
and sarcoplasmic reticulum (SR) Ca2+ load during steady-state voltage
clamp depolarization. Mean arterial pressure (MAP) and heart
weight/body weight ratio of banded (B) animals were significantly
higher than in control or sham operated animals (C). Isolated myocyte
dimensions and volume increased in parallel with whole heart
hypertrophy and elevation in MAP. However, the relation between
membrane surface area (measured by capacitance) and cell volume
(measured by laser scanning confocal microscopy) was unaltered [C:
8.9+/-0.3; B: 8.5+/-0.4 pF/pL]. No differences in the voltage
dependence of ICa activation, steady-state inactivation or recovery
from inactivation were detected between C and B myocytes. Maximal ICa
density for the two groups was also not different either under basal
conditions [C: 4.28+/-0.98; B: 4.57+/-0.60 pA/pF] or in the presence
of 1 [mu]M isoproterenol [C: 16.6+/-2.3; B: 16.5+/-2.3 pA/pF]. The
fraction of Ca2+ released from the SR by a single twitch was 55.4+/
-9.4% in C and 37.1+/-6.9% in B (not significantly different). Steady
state Ca2+ influx during a twitch was calculated in units of
[mu]mol/l non-mitochondrial volume from the integral of ICa [C:
13.4+/-0.7 [mu]M, B: 13.3+/-0.8 [mu]M]. The SR Ca2+ load was
similarly calculated by integration of Na+-Ca2+ exchange current
induced by rapid caffeine application [C: 140+/-9 [mu]M, B: 169+/-18
[mu]M]. We conclude that significant cellular hypertrophy is
associated with proportional increases in sarcolemmal ICa influx, SR
Ca2+ loading and the amount of SR Ca2+ released in this model of
pressure overload.
Received 24 July 1996; accepted in final form 30 October 1996.
APS Manuscript Number H663-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996