Role of intracellular calcium in promoting muscle damage: a strategy for controlling the dystrophic condition

Abstract

It is suggested that various muscle diseases and examples of experimentally-induced muscle damage arise because of a high calcium level in the myoplasm. When [Ca2+]i is raised experimentally in amphibian or mammaliam muscle by treatment with A23187 or caffeine, myofilament degradation follows quickly. Such a rapid action suggests the involvement of a sequence of proteolytic activity that is stimulated by a rise in [Ca2+]i. Ca2+ might either trigger protease activity directly or indirectly, or promote the release of lysosomal enzymes. A high [Ca2+]i in dystrophic muscle is believed to be the resultant of a sequence of events that is summarized in the figure. Suggestions are presented for different ways in which the steady-state position of [Ca2+]i might ultimately be controlled for the clinical amelioration of some dystrophic conditions.