Malignant hyperthermia: effects of halothane on the surface membrane.
We studied the electrical properties of intact muscle fibers from normal and malignant hyperthermia-susceptible (MHS) pigs. Resting membrane potentials, action potentials, and current-voltage relationships were measured with and without the presence of halothane. There were no changes in the resting potentials or the specific membrane conductances at any concentration of halothane in either the normal or MHS fibers. The current-voltage relationships of normal and MHS fibers did not differ. Contractures were observed in MHS muscle when the concentration of halothane was greater than or equal to 0.8%. These halothane-induced contractures were not associated with depolarization of the surface membrane. Contractures were not observed in normal muscle even at concentrations of 6.0% halothane. In contrast, halothane altered the shape of the action potentials of both MHS and normal fibers. However, these changes were significantly greater in MHS fibers, occurred at much lower concentrations, and were partially prevented by preincubation in 10 microM dantrolene.
Iaizzo
P A
PA
Department of Pharmacology, Mayo Foundation, Rochester, MN 55905.
Lehmann-Horn
F
F
Taylor
S R
SR
Gallant
E M
EM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003620:Dantrolene / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction; D009132:Muscles / Q000503:physiopathology*; D013552:Swine
D003620:Dantrolene; D006221:Halothane