Malignant hyperthermia: slow sodium current in cultured human muscle cells.
Voltage-activated ion currents were measured in cultured skeletal muscle myoballs. Cultures were generated from biopsies from patients referred for diagnosis of susceptibility to malignant hyperthermia (MH); diagnosis of susceptibility (MH+) or nonsusceptibility (MH-) was made on the basis of in vitro halothane-induced contracture of a separate piece of biopsy. Measurements of ion currents were made at room temperature in the absence of anesthetic agents, using tight-seal whole-cell recording. Fast transient Na+ currents and delayed outward K+ currents were similar in magnitude and kinetics in cells from MH+ and MH- patients. An additional slowly inactivating inward current component was commonly observed in cells from MH+ patients. This current was blockable by tetrodotoxin and was carried by Na+ but not by Ba2+. The component was less frequently observed and was of a lower magnitude in cells from MH- patients. The increased magnitude of the slow inward current observed in cultured muscle cells from MH+ patients may be a manifestation of the lesion that causes MH.
Wieland
S J
SJ
Department of Anatomy, Hahnemann University, Philadelphia, Pennsylvania 19102.
Fletcher
J E
JE
Rosenberg
H
H
Gong
Q H
QH
D002110:Caffeine / Q000494:pharmacology; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004553:Electric Conductivity; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000502:physiology / Q000503:physiopathology*; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels; D002110:Caffeine; D006221:Halothane