Troponin C, slow skeletal and cardiac muscles (TNNC1) (TNNC1)

Troponin C, slow skeletal and cardiac muscles (TNNC1) is the calcium-binding subunit of the troponin complex, which regulates the contraction of cardiac and slow-twitch skeletal muscle [2, 4]. It consists of two globular domains: a structural C-terminal domain that remains anchored to the troponin complex and a regulatory N-terminal domain that binds calcium ions during muscle activation [2, 9]. Upon binding calcium, TNNC1 undergoes a conformational change that shifts the inhibitory troponin I subunit away from the actin filament, allowing myosin to bind and initiate contraction [3, 11]. Mutations in the TNNC1 gene are associated with various forms of cardiomyopathy, including hypertrophic, dilated, and restrictive phenotypes, often leading to early-onset heart failure [4, 14]. Consequently, TNNC1 is a significant therapeutic target for cardiotonic agents known as calcium sensitizers, such as levosimendan, which enhance myocardial contractility by stabilizing the calcium-bound state of the protein without increasing intracellular calcium levels [1, 3, 13]. This mechanism is particularly valuable in treating acute heart failure as it avoids the pro-arrhythmic risks associated with traditional inotropes that elevate cytosolic calcium [3, 5].

Other names

cTnCTroponin C1TN-CTNCTNNCCMD1ZCMH13

Calcium sensitization and calcium desensitization