During calcium signaling calcium ions act as second messengers in signal transduction. Second messengers are intracellular signals that mediate physiological processes. Important physiological roles for calcium signalling include muscle contraction, and the cellular motility, including the movement of flagella and cilia. Other biochemical roles of calcium include regulating enzyme activity, ion pumps, and components of the cytoskeleton.
Signaling occurs when the cell is stimulated to release calcium ions (Ca2+) from intracellular stores. The resting concentration of Ca2+ in the cytoplasm is normally maintained in the range of 10 - 100 nM. To maintain this low concentration, Ca2+ is actively pumped from the cytosol and accumulated in the endoplasmic reticulum (ER), and sometimes in the mitochondria. Certain proteins of the cytoplasm and organelles act as buffers by binding Ca2+.
Specific signals can trigger a sudden increase in the cytoplasmic Ca2+ level up to 500 - 1 000 nM by opening channels in the endoplasmic reticulum or the plasma membrane. Many of Ca2+-mediated events occur when the released Ca2+ binds to and activates the regulatory protein calmodulin.
After cytoplasmic calcium has been depleted, Ca2+ can be imported from outside the cell by activation of SOC channels. This inflowing calcium current that results after stored calcium reserves have been released is referred to as Ca2+-release-activated Ca2+ current (ICRAC). The mechanisms through which ICRAC occurs are currently still under investigation, although two candidate molecules, Orai1 and STIM1 have been linked by several studies, and a model of store-operated calcium influx, involving these molecules, has been proposed. Recent studies have cited the phospholipase A2 beta, nicotinic acid adenine dinucleotide phosphate (NAADP), and the protein STIM 1 as possible mediators of ICRAC.
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