Calcium Signaling in the Heart.

The aim of this chapter is to discuss evidence concerning the many roles of calcium ions, Ca, in cell signaling pathways that control heart function. Before considering details of these signaling pathways, the control of contraction in ventricular muscle by Ca transients accompanying cardiac action potentials is first summarized, together with a discussion of how myocytes from the atrial and pacemaker regions of the heart diverge from this basic scheme. Cell signaling pathways regulate the size and timing of the Ca transients in the different heart regions to influence function. The simplest Ca signaling elements involve enzymes that are regulated by cytosolic Ca. Particularly important examples to be discussed are those that are stimulated by Ca, including Ca-calmodulin-dependent kinase (CaMKII), Ca stimulated adenylyl cyclases, Ca stimulated phosphatase and NO synthases. Another major aspect of Ca signaling in the heart concerns actions of the Ca mobilizing agents, inositol trisphosphate (IP), cADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate, (NAADP). Evidence concerning roles of these Ca mobilizing agents in different regions of the heart is discussed in detail. The focus of the review will be on short term regulation of Ca transients and contractile function, although it is recognized that Ca regulation of gene expression has important long term functional consequences which will also be briefly discussed.