Cellular membrane potentials and contractile threshold in mammalian skeletal muscle susceptible to malignant hyperthermia

Abstract

An increase in external K⁺ can generate contractile force in muscle, and K⁺ contractures are an established means to determine the effect of an agent on the relation between membrane potential and mechanical activity [8]. We have used K⁺-contractures to further test our hypothesis [5] that abnormal cell membrane potential responses are intrinsic to skeletal muscle of Poland China pigs susceptible to malignant hyperthermia (MHS), and a nervous system is not required to initiate malignant hyperthermia (MH). Recently it has been shown that K⁺-induced contractures in certain skeletal and cardiac muscles might not be determined only by cellular membrane potential changes predicted by the tendency for K⁺ to move in accord with its electrical and concentration gradients [3,12]. We report here that normal and diseased skeletal muscles respond differently to raised external K⁺, which supports the idea that the onset on the MH syndrome is determined by a defect associated with a site in muscle cells superficial to the cytoplasm rather than, as has been suggested, within the cell or in the nervous system [7]. In addition, we find that porcine skeletal muscles, like certain other muscles, produce much less force in K⁺ than expected from our measurements of the relationship between membrane potential and external K⁺.