Malignant Hyperthermia: Excitation-Contraction Coupling, Ca[sup]2+[r]
Release Channel, and Cell Ca[sup]2+[r] Regulation Defects.
Mickelson, James R., and Charles F. Louis.
Dept. of Veterinary Medicine, University of Minnesota, 295 Animanl
Science/Veterinary Medicine Bldg., 1988 Fitch Ave., St. Paul, Minnesota,
55108
APStracts 2:0029P, 1996.
ABSTRACT
Malignant hyperthermia (MH) is a disorder of skeletal muscle in which certain
anesthetic agents trigger a sustained elevation in myoplasmic Ca[sup]2+[r]
concentration that activates metabolic and contractile activity. This review
focuses on the biochemical and physiological alterations in the skeletal
muscle of MH-susceptible (MHS) pigs and humans that appear responsible for
this often inherited disorder. In porcine MH, these studies identified the
skeletal muscle sarcoplasmic reticulum Ca[sup]2+[r] release channel gene
([i]RYR1[r]) as the site of the defect. A mutation in this protein results in
altered excitation-contraction coupling and secondary changes in porcine
muscle structure and function. Although [i]RYR1[r] mutations have been
reported in many MHS human families, there is also significant genetic
heterogeneity, and much less is known as to the underlying mechanism
responsible for altered human myoplasmic Ca[sup]2+[r] regulation. The effects
of caffeine and anesthetic agents on MHS and normal muscle are also discussed
to better understand the basis for the in vitro clinical test for this
disorder and mechanisms responsible for the initiation and maintenance of MH
episodes in susceptible individuals. Finally, we examine the possibility of a
defect in Ca[sup]2+[r] regulation in tissues other than skeletal muscle.
Current understanding of the molecular basis of MH elegantly illustrates the
successful integration of knowledge obtained from all fields of biological and
clinical science.
APS Manuscript Number P1-6.
Article publication pending April 1996, Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996