Dantrolene sodium is able to reduce the resting ionic [Ca2+]i in muscle from humans with malignant hyperthermia.
Malignant hyperthermia (MH) is a hereditary myopathy, triggered when susceptible patients are exposed to a depolarizing muscle relaxant and/or potent volatile anesthetics. We have studied the effects of dantrolene on the free [Ca2+]i of intercostal muscle biopsies obtained from two MH-susceptible patients before and after administration of dantrolene orally (2.5 mg/kg for 3 days) and intravenously (1.0 mg/kg 2 hours before the biopsy). The free [Ca2+]i was measured by Ca2+-selective microelectrodes. The mean resting free [Ca2+]i in the MH-susceptible muscle before dantrolene treatment was 0.42 +/- 0.01 microM (mean +/- SEM, n = 12). The administration of dantrolene reduced this value to 0.27 +/- 0.01 microM (n = 14). There was no detectable difference in the resting membrane potential after dantrolene. These results represent the first direct demonstration that dantrolene is able to reduce the resting free [Ca2+]i in skeletal muscle of MH-susceptible patients.
D000328:Adult; D002118:Calcium / Q000378:metabolism*; D003620:Dantrolene / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008305:Malignant Hyperthermia / Q000188:drug therapy* / Q000378:metabolism; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism
D003620:Dantrolene; D002118:Calcium