Calcium signaling

Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors. The resting concentration of Ca2+ in the cytoplasm is normally maintained around 100 nM. This is 20,000- to 100,000-fold lower than typical extracellular concentration. To maintain this low concentration, Ca2+ is actively pumped from the cytosol to the extracellular space, the endoplasmic reticulum (ER), and sometimes into the mitochondria. Certain proteins of the cytoplasm and organelles act as buffers by binding Ca2+. Signaling occurs when the cell is stimulated to release Ca2+ ions from intracellular stores, and/or when Ca2+ enters the cell through plasma membrane ion channels. Under certain conditions, the intracellular Ca2+ concentration may begin to oscillate at a specific frequency. Specific signals can trigger a sudden increase in the cytoplasmic Ca2+ levels to 500–1,000 nM by opening channels in the ER or the plasma membrane. The most common signaling pathway that increases cytoplasmic calcium concentration is the phospholipase C (PLC) pathway. Many cell surface receptors, including G protein-coupled receptors and receptor tyrosine kinases, activate the PLC enzyme. PLC uses hydrolysis of the membrane phospholipid PIP2 to form IP3 and diacylglycerol (DAG), two classic secondary messengers. DAG attaches to the plasma membrane and recruits protein kinase C (PKC). IP3 diffuses to the ER and is bound to the IP3 receptor. The IP3 receptor serves as a Ca2+ channel, and releases Ca2+ from the ER. The Ca2+ bind to PKC and other proteins and activate them. Depletion of Ca2+ from the ER will lead to Ca2+ entry from outside the cell by activation of "Store-Operated Channels" (SOCs).