Regulation of Ca(2+)-signaling in cardiac myofilaments.

The contraction and relaxation of heart muscle cells is associated with a transient change in the intracellular level of free Ca2+. This transient reflects a release from the sarcoplasmic reticulum of Ca2+ ions that turn on the reaction of myosin cross-bridges of the thick filaments with actin of the thin filaments. Without this transient no contraction occurs. The first part of this paper is concerned with the molecular processes by which Ca2+ signals the actin-myosin reaction. It will show that the activation in reality involves release of the thin filaments from a prevailing inhibited state. The inhibited state depends on the activity of the troponin (TN) complex and tropomyosin (TM); disinhibition requires Ca(2+)-binding to TN. The second part of the paper describes evidence that the signaling process is itself modulated by the mechanical and chemical state of the myofilaments in the short term and by altered gene expression in the long term.