Effects of mg2+ on ca2+ waves and ca2+ transients of rat
ventricular myocytes.
Terada, Hajime, Hideharu Hayashi, Naohisa Noda, Hiroshi Satoh, Hideki
Katoh, Noboru Yamazaki.
The Third Department of Internal Medicine, Photon Medical Research
Center, Hamamatsu University School of Medicine, 3600 Handa-cho,
Hamamatsu 431-31, Japan
APStracts 2:0533H, 1995.
It has been shown that the occurrence of the transient inward current,
which is responsible for triggered activity, was often associated
with propagating regions of increased intracellular Ca2+
concentration ([Ca2+]i), so called "Ca2+ wave". To
investigate the mechanism of the anti-arrhythmic action of Mg2+, we
have studied the effects of high concentrations of Mg2+ on Ca2+ waves
in isolated rat ventricular myocytes. The [Ca2+]i was estimated using
the Ca2+ indicating probe, indo-1. Ca2+ waves in the myocytes,
stimulated at 0.2 Hz, were induced by the perfusion of isoproterenol
(10-7 M). High Mg2+ suppressed Ca2+ waves in a concentration
-dependent manner (36 % at 4 mM, 70 % at 8 mM, and 82 % at 12 mM). The
Ca2+ channel blocker, verapamil, also suppressed Ca2+ waves in a
similar way. In contrast with the marked depression of Ca2+
transients by verapamil, Ca2+ transients were not affected by high
Mg2+ (8 mM). High Mg2+ also reduced the frequencies of Ca2+ waves in
the absence of electrical stimulation, whereas verapamil failed to
reduce the frequencies of Ca2+ waves . The reduction of frequency of
Ca2+ waves by high Mg2+ was associated with the slowing of the
propagation velocity of Ca2+ waves. In order to examine whether the
suppressive effects of high Mg2+ on Ca2+ waves were related to an
increase in intracellular Mg2+ concentration ([Mg2+]i), the effect of
high Mg2+ solution on [Mg2+]i was examined in myocytes loaded with
mag-fura-2. An increase in [Mg2+]o from 1 mM to 12 mM increased
[Mg2+]i from 1.06+/-0.16 mM to 1.87+/-0.22 mM (p<0.01) in 30
min. To examine the effect of high Mg2+ on the amount of releasable
Ca2+ in the sarcoplasmic reticulum (SR), the effect of high Mg2+ on
the Ca2+ transient induced by a rapid application of caffeine was
examined. High Mg2+ solution increased the peak of the caffeine
-induced Ca2+ transient. These results suggest that the inhibitory
effect of Mg2+ on Ca2+ waves was not due to the inhibition of the
sarcolemmal Ca2+ channel, but could be due to a decreased propensity
for the SR to divest itself of excess Ca2+.
Received 4 November 1994; accepted in final form 11 July 1995.
APS Manuscript Number H988-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95