PORCINE MALIGNANT HYPERTHERMIA - GENOTYPE AND CONTRACTILE THRESHOLD OF IMMATURE MUSCLES

We investigated whether malignant hyperthermia (MH)-related contractil e abnormalities, such as lowered contractile threshold, were expressed in MH-susceptible (MHS) immature muscles and myotubes. Muscles from n eonatal piglets homozygous for Arg(615) (normal) or for Cys(615) (MHS) ryanodine receptor alleles, and heterozygotes were used, Intact cell bundles from piglet muscles generally were similar in contractile prop erties to adult muscles of the same genotype, Thresholds for K contrac tures in normal, heterozygous, and MHS piglet muscles (40 mmol/L, 25 m mol/L and 15 mmol/L K+, respectively) differed significantly, Cultured myotubes were subjected to a series of square pulses of varying stren gths (-50 to +50 mV) and durations (25-300 ms) using whole cell patch- clamp techniques. Threshold for contraction differed significantly amo ng the three genotypes, for example, with 300 msec pulses thresholds w ere -6.9 +/- 0.9, -12.4 +/- 1.6, and -22.6 +/- 2.6 mV for normal, hete rozygous and MHS myotubes, respectively. Thus a significantly lower th an normal threshold for contraction was expressed in MHS and heterozyg ous piglet muscles and myotubes. Further, these developmentally immatu re preparations are likely to express other differences characteristic of adult MHS muscles, and thus provide suitable preparations for clin ically relevant studies of MH-related cellular abnormalities. (C) 1996 John Wiley & Sons, Inc.