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.