Mechanisms of stretch-induced muscle damage in normal and dystrophic muscle: role of ionic changes

Abstract

Muscle damage, characterized by prolonged weakness and delayed onset of stiffness and soreness, is common following contractions in which the muscles are stretched. Stretch-induced damage of this sort is more pronounced in the muscular dystrophies and the profound muscle damage observed in these conditions may involve similar pathways. It has been known for many years that damaged muscles accumulate calcium and that elevating calcium in normal muscles simulates many aspects of muscle damage. The changes in intracellular calcium, sodium and pH following stretched contractions are reviewed and the various pathways which have been proposed to allow ion entry are discussed. One possibility is that TRPC1 (transient receptor potential, canonical), a protein which seems to form both a stretch-activated channel and a store-operated channel, is the main source of Ca(2+) entry. The mechanisms by which the changes in intracellular ions contribute to reduced force production, to increased protein breakdown and to increased membrane permeability are considered. A hypothetical scheme for muscle damage which incorporates these ideas is presented.

Figure 1. Pathways involved in stretch-induced muscle damage

Possible intracellular pathways by which stretched contractions cause reduced force production and increased membrane permeability. Dashed box indicates hypothetical mechanisms which may be involved in activating channels for Ca²⁺ entry. Dashed arrow indicates positive feedback pathway that would occur when increased membrane permeability causes elevated [Ca²⁺]_i. For further details see text. ROS, reactive oxygen species; creatine kinase (CK).