Reduced inhibitory effect of mg2+ on ca2+ release in muscle fibers
from pigs susceptible to malignant hyperthermia.
Owen, V. J., N. L. Taske & G. D. Lamb.
School of Zoology, La Trobe University, Bundoora, Victoria, 3083;
John Curtin School of Medical Research, Australian National
University, Canberra, A.C.T., 2601, Australia
APStracts 3:0244C, 1996.
The inhibitory effect of myoplasmic Mg2+ on Ca2+ release from the
sarcoplasmic reticulum (SR) was examined in mechanically-skinned
skeletal muscle fibers from pigs of different ryanodine receptor
(RyR) genotype. In fibers from pigs homozygous for the normal RyR
allele, the free [Mg2+] had to be lowered from the normal resting
level of 1mM to approximately 0.1mM in order to induce Ca2+ release
and a force response. Fibers from pigs heterozygous or homozygous for
the RyR allele associated with malignant hyperthermia (MH), needed
only a smaller reduction in free [Mg2+] to induce Ca2+ release
(reduction to 0.1-0.2mM and to >/=0.2mM, respectively). Dantrolene
(20[mu]M) counteracted the effect of this reduced Mg2+ inhibition in
MH muscle. The response of muscle fiber bundles to the caffeine
-halothane contracture (CHC) test in the three genotypes correlated
well with the responsiveness of single fibers to reduced [Mg2+].
Thus, the abnormal responsiveness of MH muscle to various stimuli may
largely result from the reduced ability of myoplasmic Mg2+ to inhibit
Ca2+ release from the SR.
Received 21 March 1996; accepted in final form 22 July 1996.
APS Manuscript Number C162-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996