on the specific characteristics of the receptor activated—both parasympathetic input and sympathetic input can be either excitatory (contractile) or inhibitory (relaxing). Cardiac muscle There are two types of cardiac muscle cells: autorhythmic and contractile. Autorhythmic cells do not contract, but instead set the pace of contraction for other cardiac muscle cells, which can be modulated by the autonomic nervous system. In contrast, contractile muscle cells (cardiomyocytes) constitute the majority of the heart muscle and are able to contract. Excitation-contraction coupling In both skeletal and cardiac muscle excitation-contraction (E-C) coupling, depolarization conduction and Ca2+ release processes occur. However, though the proteins involved are similar, they are distinct in structure and regulation. The dihydropyridine receptors (DHPRs) are encoded by different genes, and the ryanodine receptors (RyRs) are distinct isoforms. Besides, DHPR contacts with RyR1 (main RyR isoform in skeletal muscle) to regulate Ca2+ release in skeletal muscle, while the L-type calcium channel (DHPR on cardiac myocytes) and RyR2 (main RyR isoform in cardiac muscle) are not physically coupled in cardiac muscle, but face with each other by a junctional coupling. Unlike skeletal muscle, E-C coupling in cardiac muscle is thought to depend primarily on a mechanism called calcium-induced calcium release, which is based on the junctional structure between T-tubule and sarcoplasmic reticulum. Junctophilin-2 (JPH2) is essential to maintain this structure, as well as the integrity of T-tubule. Another protein, receptor accessory protein 5 (REEP5), functions to keep the normal morphology of junctional SR. Defects of junctional coupling can result from deficiencies of either of the two proteins. During the process of calcium-induced calcium release, RyR2s are activated by a calcium trigger, which is brought about by the flow of Ca2+ through the L-type calcium channels. After this, cardiac muscle tends to exhibit diad structures, rather than triads. Excitation-contraction coupling in cardiac muscle cells occurs when an action potential is initiated by pacemaker cells in the sinoatrial node or atrioventricular node and conducted to all cells in the heart via gap junctions. The action potential travels along the surface membrane into T-tubules (the latter are not seen in all cardiac cell types) and the depolarisation causes extracellular to enter the cell via L-type calcium channels and possibly sodium-calcium exchanger (NCX) during the early part of the plateau phase. Although this Ca2+ influx only count for about 10% of the Ca2+ needed for activation, it is relatively larger than that of skeletal muscle. This