Skeletal and cardiac muscle calcium transport regulation in health and disease

In healthy muscle, the rapid release of calcium ions (Ca2+) with excitation-contraction (E-C) coupling, results in elevations in Ca2+ concentrations which can exceed 10-fold that of rest-ing values. The sizable transient changes in Ca2+ concentrations are necessary for the ac-tivation of signaling pathways, which rely on Ca2+ as a second messenger, including those involved with force generation, fiber type distribution and hypertrophy. However, prolonged elevations in intracellular Ca2+ can result in the unwanted activation of Ca2+ signaling path-ways that cause muscle damage, dysfunction, and disease. Muscle employs several cal-cium handling and calcium transport proteins that function to rapidly return Ca2+ concen-trations back to resting levels following contraction. This review will detail our current under-standing of calcium handling during the decay phase of intracellular calcium transients in healthy skeletal and cardiac muscle. We will also discuss how impairments in Ca2+ transport can occur and how mishandling of Ca2+ can lead to the pathogenesis and/or progression of skeletal muscle myopathies and cardiomyopathies.