Skeletal muscle troponin complex (sTn) (sTn)

Skeletal muscle troponin is a heterotrimeric protein complex located on the thin filaments of skeletal muscle fibers, consisting of three subunits: troponin C (calcium-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding) [1]. It plays a critical role in the regulation of muscle contraction by acting as a calcium-sensitive switch that controls the interaction between actin and myosin [2]. In the absence of calcium, the complex inhibits the binding of myosin to actin; upon calcium binding to troponin C, a conformational change occurs that shifts tropomyosin, allowing cross-bridge cycling and force production [3]. This complex is a significant therapeutic target for neuromuscular and respiratory diseases characterized by muscle weakness, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) [4]. Pharmacological activators, specifically fast skeletal muscle troponin activators (FSTAs), are designed to increase the sensitivity of the sarcomere to calcium, thereby enhancing muscle power and endurance at submaximal levels of nerve stimulation [5]. While these drugs aim to improve physical function and respiratory capacity, challenges include achieving selectivity over cardiac troponin and managing central nervous system side effects like dizziness [6].

Other names

Fast skeletal muscle troponinSlow skeletal muscle troponinTroponin complex (skeletal)sTnTroponin C1Troponin I2Troponin T3 [1, 2]

Fast skeletal muscle troponin activators (FSTAs) increase the sensitivity of the troponin complex to calcium by slowing the rate of calcium dissociation from troponin C, which increases the number of active actin-myosin cross-bridges at any given submaximal calcium concentration [3, 5].