Malignant Hyperthermia and Central Core Disease: Disorders of Ca 2 Release Channels

Abstract

Muscle contraction and relaxation result from the interplay between two elaborate cellular structures and the small molecule, Ca2+, which cycles between them. The contractile elements are formed as short, repeating segments referred to as sarcomeres (1,2). Within sarcomeres, longitudinally aligned, centrally located, thick filaments contain myosin, the adenosine triphosphate (ATP)-activated motor for the generation of contractile force (Figure 1). Thick filaments interdigitate between similarly aligned thin filaments that are anchored at either end of the sarcomere, but free in the center, forming bipolar arrays. The interaction between myosin molecules, oriented in a bipolar manner within thick filaments, and actin molecules in the two opposed thin filaments, results in shortening of the sarcomere as the thin filaments are drawn toward the center of the sarcomere. Relaxation results from release of the interaction between thin and thick filaments. In skeletal and cardiac muscle, the physical interactions between actin and myosin are possible only when Ca2+ is bound to a low molecular weight, high affinity Ca2+ binding protein, troponin C (3). Troponin C is located within a heterotrimeric, globular troponin complex, attached to filamentous tropomyosin, so that it forms a regulatory structure within the thin filament.