Cardiac troponin C (cTnC) (cTnC)

Cardiac troponin C (cTnC) is the calcium-sensing component of the troponin complex, which regulates the contraction of cardiac and slow-twitch skeletal muscle [1]. It is composed of two globular domains: the N-terminal regulatory domain and the C-terminal structural domain, connected by a flexible alpha-helical linker [2]. The C-terminal domain (CTD) contains two high-affinity EF-hand motifs (Sites III and IV) that are typically occupied by calcium or magnesium ions, serving to anchor cTnC to the troponin I and troponin T subunits [1]. Mutations in the TNNC1 gene, particularly within the CTD, are associated with various forms of cardiomyopathy, including hypertrophic and dilated phenotypes, by altering the calcium sensitivity of the myofilament [4]. Pharmacologically, cTnC is a target for calcium sensitizers such as levosimendan and pimobendan, which enhance myocardial contractility in heart failure patients [3]. While many sensitizers interact with the N-domain, the CTD is also a binding site for drugs like bepridil and certain calmodulin antagonists, which can modulate the overall stability and function of the troponin complex [2, 4]. Targeting this protein allows for increased cardiac output without the pro-arrhythmic risks associated with elevated intracellular calcium levels [4].

Other names

Troponin C1, slow skeletal and cardiac musclesTNNC1TNCCardiac troponin C, C-terminal domainTroponin C1CMD1ZCMH13

Calcium sensitization of the myofilament by stabilizing the calcium-bound conformation of troponin C, thereby enhancing the interaction between the thin and thick filaments without increasing intracellular calcium concentrations [3, 4].