Calcium binding kinetics of troponin C strongly modulate cooperative activation and tension kinetics in cardiac muscle

►Cooperative cardiac thin filament activation depends on cTnC Ca2+ binding kinetics. ►cTnC Ca2+ dissociation rate (koff) affects acto-myosin binding but not cycling. ►Altering koff affects Ca2+ sensitivity of isometric tension development. ►Increasing koff can decrease the rate of contractile activation. ►Decreasing koff can increase the duration of isometric relaxation.