Nat. Rev. Cardiol. doi:10.1038/nrcardio.2016.140 Figure 7 Calcium handling and the actin myosin crossbridge cycle in cardiac muscle Figure 7 | Calcium handling and the actin myosin crossbridge cycle in cardiac muscle. a | Calcium handling in the cardiomyocyte. b | The myosin head binds strongly to ATP. ATP is hydrolysed to ADP and inorganic phosphate (Pi), which remain bound to myosin; the energy released locks the myosin head into a pre-stroke configuration. Voltage-gated L-type Ca2+ channels open during phases 0 and 1 of the cardiac myocyte action potential, allowing a small influx of Ca2+ ions. This influx in turn activates cardiac ryanodine receptors (RyR), triggering much greater release of stored, calsequestrin-bound Ca2+ ions from the sarcoplasmic reticulum (calcium-induced calcium release, CICR). The rapidly rising cytosolic calcium activates troponin C (TnC), which pulls tropomyosin out of its groove on the actin filament. Binding sites for myosin are now lying exposed on the actin filament. Myosin–ADP–Pi binds to actin, weakly at first. Pi is subsequently released, resulting in stronger binding of myosin–ADP to actin. This weak-to-strong transition is generally the rate-limiting step in the actin–myosin crossbridge cycle. The myosin power stroke happens next (force-producing state). Subsequent release of ADP frees the myosin head to dissociate from actin and bind preferentially to ATP again. Relaxation of the cardiac myocyte during diastole is dependent on calcium being extruded from the cell by the Na+/Ca2+ exchanger and the sarcolemmal Ca2+ pump, and sequestered back into the sarcoplasmic reticulum by the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) pump, which is inhibited by dephosphorylated phospholamban (PLB). TnI, troponin I; TnT, troponin T. Sen-Chowdhry, S. et al. (2016) Update on hypertrophic cardiomyopathy and a guide to the guidelines Nat. Rev. Cardiol. doi:10.1038/nrcardio.2016.140