Impaired Calcium Homeostasis and Calcium Antagonists in Muscle Diseases

Abstract

The electrical excitation of the muscle plasma membrane following a nerve impulse spreads into the T-tubule system. The electrical signal is then transferred to the sarcoplasmic reticulum, and large amounts of Ca²⁺ stored in its lumen are released into the cytosol. In the resting state at low cytosolic Ca²⁺ concentrations (about 10⁻⁷ M), tropomyosin sterically blocks the interaction of myosin heads with actin. When the cytosolic Ca²⁺ level is raised up to 10⁻⁵ M following the electrical excitation, free Ca²⁺ interacts with troponin, resulting in a conformational change of the tropomyosin, allowing the myosin heads to interact with actin. Subsequently, the Ca²⁺ concentrations of the myofibrillar compartment are rapidly restored to the resting level by uptake of Ca²⁺ into the sarcoplasmic reticulum through the Ca²⁺-Mg²⁺ ATPase located in the sarcoplasmic reticulum [19].