Altered E-C coupling in triads isolated from malignant hyperthermia- susceptible porcine muscle

Triad vesicles were isolated from normal (N) and homozygous malignant hyperthermia-susceptible (MHS) porcine skeletal muscle, and two types of sarcoplasmic reticulum Ca²⁺ release were investigated: 1) polylysine- induced Ca²⁺ release (direct stimulation of the junctional foot protein), and 2) depolarization-induced Ca²⁺ release (stimulation of the junctional foot protein via the dihydropyridine receptor). At submaximal 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 compared at a given grade of T-tubule depolarization, the release rate was always 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 indirectly via a depolarization-induced activation of the T- tubule dihydropyridine receptor.