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 influx causes a small local increase in intracellular . The increase of intracellular is detected by RyR2 in the membrane of the sarcoplasmic reticulum, which releases in a positive feedback physiological response. This positive feedback is known as calcium-induced calcium release and gives rise to calcium sparks ( sparks). The spatial and temporal summation of ~30,000 sparks gives a cell-wide increase in cytoplasmic calcium concentration. The increase in cytosolic calcium following the flow of calcium through the cell membrane and sarcoplasmic reticulum is moderated by calcium buffers, which bind a large proportion of intracellular calcium. As a result, a large increase in total calcium leads to a relatively small rise in free .