Skeletal muscle excitation-contraction coupling. II. Plasmalemma voltage control of intact bundle contractile properties in normal and malignant hyperthermic muscles

Abstract

Bundles of cells, intact from tendon to tendon, were dissected from muscles of normal and malignant hyperthermia susceptible (MHS) pigs. Intact bundles were stimulated either (1) electrically, to elicit twitches and tetani, or (2) ionically with elevated extracellular K+ (K+0), to elicit K-contractures. Maximal tetanic force was the same for MHS and normal intact bundles. In MHS muscles, when responses were elicited from control resting plasmalemma polarization (4 mM K+0), twitches and K-contractures were significantly larger and the K-contracture activation curve was shifted towards lower [K+]0 with respect to normal bundles. Resting hyperpolarization (2 mM K+0) selectively reduced MHS twitch force to normal and K-contracture force toward normal. For K-contracture and twitches, there was a range of K+0 concentrations (7-10 mM), representing resting depolarization, which enhanced subsequent twitch and K-contracture magnitude in both MHS and normal intact bundles as compared to responses elicited from control (4 mM K+0). These results are consistent with the hypothesis that resting plasmalemma voltage sets the gain of sarcoplasmic reticulum calcium release in MHS and normal intact bundles independent of type of stimulation and suggest that a defect in this mechanism may be responsible for the enhanced twitches and K-contractures of MHS muscles.