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Troponin C, slow skeletal and cardiac muscle (TNNC1) is the calcium-binding subunit of the troponin complex in cardiac and slow-twitch skeletal muscle. It serves as the primary molecular sensor for intracellular calcium, initiating muscle contraction by undergoing a conformational change upon calcium binding that allows the interaction between actin and myosin filaments. Mutations in the TNNC1 gene are associated with several forms of cardiomyopathy, including hypertrophic, dilated, and restrictive types, often leading to early-onset heart failure or sudden cardiac death. As a therapeutic target, TNNC1 is modulated by calcium sensitizers such as levosimendan, which increase the affinity of the protein for calcium or stabilize its active state. These drugs aim to improve cardiac output in heart failure patients without the adverse effects associated with increased intracellular calcium levels, such as increased oxygen consumption or triggered arrhythmias. Additionally, TNNC1 is identical in both cardiac and slow skeletal muscle, meaning that drugs targeting this protein may have systemic effects on skeletal muscle function. Research continues to explore TNNC1 as a target for precision medicine to correct specific mutation-induced defects in calcium sensitivity.
Calcium sensitization via stabilization of the open conformation of the N-terminal domain
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