Skeletal muscle excitation-contraction coupling. I. Transverse tubule control of peeled fiber Ca2+-induced Ca2+ release in normal and malignant hyperthermic muscles.

Porcine skeletal muscle fibers were studied to determine if the defect in malignant hyperthermia involves transverse tubule (TT) to sarcoplasmic reticulum (SR) communication. Peeled (mechanically skinned) skeletal muscle fibers from normal and malignant hyperthermia susceptible (MHS) pigs were stimulated with Cl- to ionically depolarize transverse tubules and thereby trigger Ca2+ release from SR. Caffeine was used to directly stimulate the Ca2+-induced Ca2+ release mechanism (CaIR) of the sarcoplasmic reticulum. Calcium released from internal fiber stores was monitored as Ca2+-activated isomeric force generation in the form of tension transients. Cl- -induced tension transients result from a primary component of Ca2+ release which triggers a secondary CaIR component; CaIR and caffeine contractures were eliminated by procaine. The primary component of Cl- -induced SR Ca2+ release was indistinguishable for MHS and normal skeletal peeled fibers at all TT resting and Cl- stimulation conditions. Only the magnitude of the secondary CaIR component was significantly larger in MHS fibers. The [Ca2+] threshold for secondary CaIR was lowered by resting TT depolarization in both normal and MHS fibers. Conditions for resting TT hyperpolarization selectively reduced the magnitude of the secondary CaIR component of MHS fibers, making them indistinguishable from normal.