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THE EFFECT OF THE CALCIUM ION ANTAGONIST 8‐(N,N‐DIETHYLAMINO)‐OCTYL‐3,4,5‐TRIMETHOXYBENZOATEON MALIGNANT HYPERPYREXIA‐SUSCEPTIBLE PORCINE SKELETAL MUSCLE
Author(s) -
Sullivan J. S.,
Galloway G. J.,
Denborough M. A.
Publication year - 1983
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1983.tb00227.x
Subject(s) - medicine , chemistry , calcium , endocrinology , antagonist , muscle contracture , skeletal muscle , halothane , endoplasmic reticulum , caffeine , contraction (grammar) , muscle contraction , excitation–contraction coupling , biochemistry , anatomy , receptor , organic chemistry
SUMMARY 1. In malignant hyperpyrexia susceptible (MHS) porcine skeletal muscle, a low concentration (100 μmol/1) of the calcium ion antagonist 8‐(N,N‐diethyl‐amino)‐octyl‐3,4,5‐trimethoxybenzoate (TMB‐8) inhibited KCl‐induced contractures, but potentiated contractures induced by halothane, caffeine and succinylcholine. 2. Higher concentrations of TMB‐8 (333 μmol/1 to 1 mmol/1) contracted MHS muscle, but had little effect on muscle tension in control preparations. 3. Treatments which inhibit excitation‐contraction coupling abolished TMB‐8‐induced hyper‐reactivity in MHS muscle. 4. TMB‐8 (50 μmol/1 and 1 mmol/1) did not alter 45 Ca 2+ levels in actively loaded microsomal preparations from MHS swine. 5. These results suggest that in malignant hyperpyrexia the primary abnormality occurs proximal to the release of calcium from the sarcoplasmic reticulum, probably at the level of excitation‐contraction coupling.