ALTERED E-C COUPLING IN TRIADS ISOLATED FROM MALIGNANT HYPERTHERMIA-SUSCEPTIBLE PORCINE MUSCLE

Triad vesicles were isolated from normal (Ni and homozygous malignant hyperthermia-susceptible (MHS) porcine skeletal muscle, and two types of sarcoplasmic reticulum Ca2+ release were investigated: 1) polylysin e-induced Ca2+ release (direct stimulation of the junctional foot prot ein), and 2) depolarization-induced Ca2+ release (stimulation of the j unctional foot protein via the dihydropyridine receptor). At submaxima l concentrations of polylysine, the rates of induced Ca2+ release from the MHS triads were greater than from normal triads. The T tubules of polarized triads were depolarized by the K+-to-Na+ ionic replacement protocol. Higher grades of T-tubule depolarization resulted in higher rates of Ca2+ release from both MHS and normal triads but, when compar ed at a given grade of T-tubule depolarization, the release rate was a lways greater from the MHS than from normal triads. Thus the activity of the SR Ca2+ release channel is always higher in MHS than in normal muscle at a given submaximal dose of release trigger. This difference is observed when the channel is stimulated directly by polylysine or i ndirectly via a depolarization-induced activation of the T-tubule dihy dropyridine receptor.