The force to maintain cardiac output is generated by contraction and relaxation of cardiomyocytes. The central regulator of cardiac contractility is the common second messenger Ca2+. Altering the Ca2+ transient and altering the sensitivity of the myofilaments to Ca2+ are two main ways to increase the strength of cardiac contraction. Ca2+ generates its signals by changing intracellular concentrations maintained by pumps, exchangers, and channels. In cardiomyocytes, there is a large internal store of Ca2+ in the sarcoplasmic reticulum (SR), which is induced to release a large amount of Ca2+ following a small increase of extracellular Ca2+ into the cytosol. Increased cytosolic Ca2+ concentration initiates contraction by inducing conformational changes in myofilament proteins. That Ca2+ must then be removed from the cytosol to allow for relaxation. The decreased contractility associated with heart failure is likely the result of alterations in myocyte Ca2+ regulation and/or alterations in contractile proteins.
Ca2+ is the central regulator of cardiac contractility. As illustrated in the top section, Ca2+ generates signals by changing internal and external concentrations. In the heart there is a large internal store of Ca2+ in the SR. During contraction (middle section), a small increase of extracellular Ca2+, mediated by the L-type Ca2+ channel, induces a much larger release of Ca2+ into the cytosol from the SR. Increased cytosolic Ca2+ initiates contraction by binding its effector TnC allowing for crossbridge formation. Ca2+ removal in relaxation (bottom section) is carried out primarily by the action of SERCA2a and NCX, although the extent that each contributes varies between species.