Nitroxyl effects on myocardium provide new insights into the significance of altered myof ilament response to calcium in the regulation of contractility

摘要

The idea that cardiac sarcomeres are not passive slaves to membrane related mechanisms modifying Ca~(2+) fluxes is generally accepted. There is substantial evidence that fundamental regulatory mechanisms including the Frank-Starling mechanism and neuro-humoral control of cardiac dynamics involve alterations in Ca~(2+) binding to troponin C (TnC) or transduction of the Ca-TnC signal to the promotion of ATP hydrolysis, force and shortening (Solaro, 2001; Kobayashi & Solaro 2005). In testimony to the recognition of the relative significance of these potential mechanisms in control of cardiac contractility, there has been a long-standing effort to develop inotropic agents acting directly on the myofilaments to modify their response to Ca~(2+) (Kass & Solaro, 2006).