Enhanced mobilization of intracellular Ca2+ induced by halothane in hepatocytes isolated from swine susceptible to malignant hyperthermia

Halothane, in a dose-dependent manner, induced the release of intracellular Ca2+ in hepatocytes prepared from swine. The magnitude of the release induced by halothane was greater for hepatocytes prepared from animals susceptible to malignant hyperthermia (MH) than for those from normal swine. Two di...

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Published in:Anesthesiology (Philadelphia) 1991-03, Vol.74 (3), p.531-538
Main Authors: IAIZZO, P. A, SEEWALD, M. J, OLSEN, R, WEDEL, D. J, CHAPMAN, D. E, BERGGREN, M, EICHINGER, H. M, POWIS, G
Format: Article
Language:English
Subjects:
Anesthetics. Neuromuscular blocking agents
Animals
Biological and medical sciences
Calcium - metabolism
Disease Susceptibility
Halothane - pharmacology
In Vitro Techniques
Ions
Liver - cytology
Liver - drug effects
Liver - metabolism
Malignant Hyperthermia - physiopathology
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Swine
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Summary:Halothane, in a dose-dependent manner, induced the release of intracellular Ca2+ in hepatocytes prepared from swine. The magnitude of the release induced by halothane was greater for hepatocytes prepared from animals susceptible to malignant hyperthermia (MH) than for those from normal swine. Two different methods were used to ascertain the release of Ca2+ induced by halothane: 1) the release of 45Ca2+ from nonmitochondrial stores of saponin-permeabilized hepatocytes was measured; and 2) changes in luminescence from intact hepatocytes loaded with the Ca2(+)-sensitive photoprotein aequorin were recorded. It was also observed that, although 1,4,5-inositol trisphosphate (IP3), guanosine-5-triphosphate, and arachidonic acid all induced a significant release of 45Ca2+ from permeabilized swine hepatocytes, only the quantities of 45Ca2+ released by IP3 were significantly greater for the hepatocytes prepared from the animals susceptible to MH. These data indicate an abnormal Ca2+ homeostasis in hepatocytes isolated from swine susceptible to MH, which supports the hypothesis that membrane systems from multiple organs may be affected in this genetic disorder.
ISSN:0003-3022
1528-1175
DOI:10.1097/00000542-199103000-00023