Ultrastructural evidence for loss of calcium homeostasis in exercised skeletal muscle.

Muscle injury has been documented following eccentric exercise bouts in skeletal muscle (Faulkner 1985, Duan et al. 1988, Lieber & Fride!n 1988). Insights into the early events causing muscle injury have been obtained from mechanical studies (Lieber & Fride!n 1993, Warren et al. 1993) as well as immunohistochemical studies of cellular and extracellular proteins (Lieber et al. 1996). From these studies has emerged the concept that a very early or even initial event associated with eccentric exercise is the loss in cellular calcium homeostasis. Indirect evidence for this phenomenon crosses experimental methods and exercise models including increased mitochondrial calcium content in rats subjected to downhill running (Duan et al. 1990), increased activity of the calcium activated neutral protease calpain after running in rats (Belcastro 1993), loss of cellular integrity with eccentric contraction of mouse muscle in vitro (Petrof et al. 1993), and selective loss of the intermediate filament protein desmin, after only 5 min of eccentric activation in rabbit tibialis anterior (TA) muscle (Lieber et al. 1996). The most common ultrastructural change accompanying eccentric exercise is the disruption of the Zdisk structure with concomitant loss of myofibrillar register (Fride!n et al. 1981). However, in this report, we present unique ultrastructural observations that may link the loss of calcium homeostasis to initial muscle injury. Eighteen rabbits were anaesthetized with a subcutaneous injection of a ketamine-xylazine-acepromazine cocktail (50, 5 and 1 mg kg−" body mass, respectively) and maintained on halothane anaesthesia. The distal tibialis anterior tendon was secured to dual-