CHAPTER 30 – Mechanisms Regulating Cardiac Myofilament Response to Calcium

Membrane control of the amounts and rates of Ca 2+ movements to and from the myofilaments is a powerful mechanism of regulating cardiac output. This chapter focuses on various mechanisms that control the cardiac myofilament response to calcium. These mechanisms are significant in the intrinsic control of the heart by Starling's law, which appears to involve length dependent myofilament activation. Extrinsic control by the autonomic nervous system also involves changes in the myofilament response to Ca 2+ . Apart form these, ischemia, reperfusion injury, stunning, and heart failure may also involve major changes in the myofilament response to Ca 2+ . Isoform shifts of myofilament proteins also modulate the response to Ca 2+ in physiological and pathological states, and emerging evidence shows that familial hypertrophic cardiomyopathy is a sarcomeric disease that is genetically linked to missense mutations in the crossbridge and in the regulatory proteins TnT and Tm. During short-term physiological changes, such as moderate exercise, the chemical state of the myofilaments is modified by covalent phosphorylation that is regulated through Ca 2+ and cyclic nucleotide pathways. Three key proteins that are substrates for these cAMP and/or Ca 2+ -dependent kinases are cTnI of the thin filament, myosin-binding protein C (MyBP-C), and myosin light chain 2 (MLC2) of the thick filament.