Skeletal and cardiac muscle calcium transport regulation in health and disease

In healthy muscle, the rapid release of calcium ions (Ca(2+)) with excitation–contraction (E-C) coupling, results in elevations in Ca(2+) concentrations which can exceed 10-fold that of resting values. The sizable transient changes in Ca(2+) concentrations are necessary for the activation of signaling pathways, which rely on Ca(2+) as a second messenger, including those involved with force generation, fiber type distribution and hypertrophy. However, prolonged elevations in intracellular Ca(2+) can result in the unwanted activation of Ca(2+) signaling pathways that cause muscle damage, dysfunction, and disease. Muscle employs several calcium handling and calcium transport proteins that function to rapidly return Ca(2+) concentrations back to resting levels following contraction. This review will detail our current understanding of calcium handling during the decay phase of intracellular calcium transients in healthy skeletal and cardiac muscle. We will also discuss how impairments in Ca(2+) transport can occur and how mishandling of Ca(2+) can lead to the pathogenesis and/or progression of skeletal muscle myopathies and cardiomyopathies.