Effects of [ca2+]i, sr ca2+ load and rest on ca2+ spark frequency
in ventricular myocytes.
Satoh, Hiroshi, Lothar A. Blatter, and Donald M. Bers.
Department of Physiology, Loyola University Chicago, 2160 South
First Avenue, Maywood IL 60153
APStracts 3:0326H, 1996.
In heart, spontaneous local increases in cytosolic Ca2+ concentration
([Ca2+]i) called "Ca2+ sparks" may be fundamental events
underlying both excitation-contraction coupling and resting Ca2+ leak
from the sarcoplasmic reticulum (SR). In this study resting Ca2+
sparks were analyzed in rabbit and rat ventricular myocytes with
laser scanning confocal microscopy and the fluorescent Ca2+ indicator
fluo 3. During the first 20 sec of rest after regular electrical
stimulation, both the frequency of Ca2+ sparks and SR Ca2+ content
gradually decreased in rabbit. When rabbit SR Ca2+ content was
decreased by reduction of stimulation rate, the initial resting spark
frequency was also decreased even though resting [Ca2+]i was
unchanged. The rest-dependent decrease in spark frequency in rabbit
cells was prevented by inhibition of Na+-Ca2+ exchange (which also
prevents SR Ca2+ depletion during rest). These results suggest that
elevation of SR Ca2+ content can increase Ca2+ spark frequency. In
contrast to rabbit cells, 20 sec of rest produced a gradual increase
in spark frequency in rat cells, although SR Ca2+ content was
constant and Ca2+ influx was completely prevented. This indicates
that there is a time-dependent increase in spark probability during
rest that is independent of [Ca2+]i or SR Ca2+. This effect was also
apparent in rabbit cells when SR Ca2+ depletion was prevented by
blocking Na+-Ca2+ exchange. Stimulation of Ca2+ extrusion via Na+
-Ca2+ exchange in the rat (by Ca2+-free superfusion, which slowly
depletes SR Ca2+ content) converted the normal rest-dependent
increase in spark frequency to a decrease. The amplitude of
individual Ca2+ sparks increased with increasing SR Ca2+ content. In
the Ca2+-overloaded state, fusion of sparks or long-lasting localized
increases of [Ca2+]i were observed with increased spark frequency. We
conclude that the resting frequency of Ca2+ sparks can be
independently affected by changes in SR Ca2+ content, [Ca2+]i or rest
period. The latter may reflect recovery of the SR Ca2+ release
channels from inactivation or adaptation.
Received 8 April 1996; accepted in final form 15 July 1996.
APS Manuscript Number H310-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996