Biochemistry and physiology of cardiac muscle

The heart is composed of muscle cells (cardiomyocytes) that account for most of the heart mass and generate its pumping force. Other cell types (fibroblasts, vascular endothelial cells, vascular smooth muscle cells, immune cells) and the extracellular matrix also play key roles in cardiac function, in both health and disease. Excitation-contraction coupling links the electrical activation of cardiomyocytes to cellular contraction. Calcium is a key second messenger in this process; its entry into the cell triggers further calcium release from the sarcoplasmic reticulum, which then activates the contractile machinery. Subsequent reduction in calcium concentration brings about cardiac relaxation, which is necessary for the heart to refill. Calcium also regulates other critical processes in the heart, including transcription of genes and the matching of energy supply from the mitochondria with cellular demand. In health, the contractile function of the heart is regulated by several factors, including its loading conditions, autonomic influences and many locally produced autocrine/paracrine agents. These factors alter contractile strength through two main mechanisms: modulation of the calcium transient within cardiomyocytes, and/or changes in myofilament sensitivity to calcium.