Dynamics of myocyte sarcomere activation and intracellular Ca²⁺ during a heartbeat. (A) Top: An electrocardiogram summarizes the depolarization of the atria (p) and ventricles (qrs) and the repolarization of the ventricles (t). Middle: The solid line shows volumes during the beat in which the LV ejects a stroke volume equal to the difference between the LV end diastolic volume (LVEDV) and the LV end systolic volume (LVESV). The dashed line shows an estimate of the changes in sarcomere length during the changes in LV volume. Bottom: The dashed line shows the Ca²⁺ release in the sarcoplasm coupled to the depolarization wave. Ca²⁺ rises, binds to cTnC triggering sarcomere tension and shortening, and then falls with reuptake. The solid line shows the associated rise and fall in LVP. (B) C-zone molecular interactions among sarcomere proteins during the heartbeat. Left:In diastole before Ca²⁺ release, crossbridges are predominantly in SRX, with a small population interacting with the thin filament in a weakly binding state. Thin filament regulatory units are predominantly in the B-state with some in a C-state promoted by interactions with the N terminus of cMyBP-C at the actin-Tm interface. Middle: Upon Ca²⁺ release, and Ca²⁺ binding to cTnC promotes the C-state in a cooperative process among thin filament regulatory units. Cycling crossbridges become active, thin filaments populate the O-state (or M-state), and tension and pressure rise. Right: Tension and pressure are sustained by force-generating crossbridges during ejection. With deactivation of the thin filaments, tension and pressure fall, but the rate of detachment of the ensemble of myosins lags the Ca²⁺-reuptake kinetics, leading to residually active regulatory units in thin filaments. A is adapted with permission from RadioGraphics (Sheth et al., 2015), with the addition of the sarcomere length (Aguirre et al., 2014) and the Ca²⁺ pulse (Allen and Kurihara, 1982) time series. See text for further discussion. Isovol., isovolumic.