In vivo induced malignant hyperthermia in pigs. III. Localization of calcium in skeletal muscle mitochondria by means of electronmicroscopy and microprobe analysis.

Biceps femoris muscle biopsies of malignant hyperthermia susceptible (MH+) and non-susceptible (MH-) Dutch Landrace pigs were studied ultrastructurally, and exchangeable calcium was demonstrated, using the antimonate precipitation technique in combination with electron probe x-ray microanalysis. Biopsies were taken before and during the administration of halothane-plus-succinylcholine and after dantrolene sodium treatment of the animals. MH+ muscle, taken before the MH triggering, showed a high proportion (about 35%) of cells with supercontraction. Both MH+ and MH- muscle had broad but nearly identical ranges of cell diameter. Core-like structures were occasionally present in muscle from MH+ pigs. Muscle mitochondria from the MH+ pigs accumulated large amounts of calcium in their matrix compartment during the halothane-plus-succinylcholine induced MH crisis. This calcium loading in the course of time caused swelling and structural damage to the mitochondria. Skeletal muscle mitochondria from MH- pigs did not show such a reaction pattern on challenge with halothane and succinylcholine. It is concluded that in MH+ pigs the challenge brings about an increase in myoplasmic free calcium, which is predominantly due to calcium influx from the extracellular fluid. This rise in cytosolic calcium causes the mitochondria to accumulate the cation in an energy-dependent way. These findings are discussed in relation to the diverging halothane and caffeine contraction responses of aerobic type I and anaerobic type II muscle fibres.