Figure 1: Schematic representation of excitation, contraction and relaxation in skeletal muscle. (1) Motoneuron activity triggers sarcolemmal depolarization generating an action potential that propagates throughout the sarcolemma and enters the T-tubule system. (2) Dihydropyridine receptor (DHPR) acts as a sensor of the action potential and undergoes a voltagedriven conformational change that (3) triggers activation and opening of the ryanodine receptor 1 (RyR1) with the consequent release of calcium from the sarcoplasmic reticulum. DHPR and RyR1 are located in the T-tubules and junctional sarcoplasmic reticulum, respectively. (4) In the sarcoplasm, calcium binding to troponin leads to tropomyosin displacement from myosin-binding sites on actin filaments enabling the formation of cross-bridge interactions between thick (myosin) and thin (actin) filaments with the consequent contraction of the sarcomere. (5) Sarcoplasmic endoplasmic reticulum Ca2+ ATPase 1 (SERCA1) is activated by elevated cytosolic calcium concentration and catalyzes the ATP-dependent transport of calcium from the cytosol to the lumen of the sarcoplasmic reticulum. Calcium withdraw from the myofibrils leads to the restoration of the tropomyosin mediated inhibition of actin–myosin interaction and therefore to muscle relaxation. SR, sarcoplasmic reticulum; DHPR, dihydropyridine receptor: RyR1, ryanodine receptor 1.