Regulation of myocardial contractility

The definition of myocardial contractility remains complex and its exact measurement remains difficult, especially in the intact heart. Measurement of load independent effects requires sophisticated equipment and preparations that are not applicable to clinical practice. At present, the more attractive concept is to think in terms of the calcium-contractile protein interaction, especially at the level of calcium-troponin-C, Either an increased supply of calcium is required to bind to the regulatory site on troponin-C, or modifications in troponin-C are required to promote interaction with the contractile system at the same level of cytosolic calcium. In other words, contractility can best be conceived of as the calcium-contractile protein interaction. There are, in addition, other sites at which calcium can act, such as by enhancing the myosin ATPase activity. Calcium-dependent phosphorylation of myosin light chains can also occur but is probably of much greater importance in vascular smooch muscle. Once calcium has interacted with troponin-C to promote the strong binding state, the crossbridge interaction has a cooperative effect whereby any attachment of crossbridges enhances binding of calcium to troponin-C. Hypothetically, even those troponin-C molecules not being activated by calcium can by this mechanism participate in the contractile process.