Please help improve this article by expanding it. Further information might be found on the talk page. (January 2007)

Calcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory affects on many enzymes and proteins. Calcium can act in signal transduction after influx resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.

Contents 1 Calcium signaling through ion channels 2 Calcium as a secondary messenger 3 See also 4 References 5 Further reading

[edit] Calcium signaling through ion channels

Movement of calcium ions from the extracellular compartment to the intracellular compartment alters membrane depolarisation. This is seen in the heart, during the plateau phase of ventricular contraction. In this example, calcium acts to maintain depolarisation of the heart.

[edit] Calcium as a secondary messenger

Important physiological roles for calcium signaling include muscle contraction, and 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.^[1]

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 "Store Operated Channels" (SOCs). 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,^[2] nicotinic acid adenine dinucleotide phosphate (NAADP),^[3] and the protein STIM 1^[4] as possible mediators of ICRAC.

[edit] See also

• Nanodomain

[edit] References

[edit] Further reading

• Petersen, Ole H (2005). "Ca2+ signalling and Ca2+-activated ion channels in exocrine acinar cells". Cell Calcium 38 (3-4): 171–200. doi:10.1016/j.ceca.2005.06.024. PMID 16107275. 

v • d • e Cell signaling Key concepts Signal transduction - Apoptosis - Second messenger system (Ca2+ signaling, Lipid signaling) Processes Paracrine - Autocrine - Juxtacrine - Neurotransmitters - Endocrine (Neuroendocrine) - Intracrine Signaling pathways Hedgehog signaling pathway - Wnt signaling pathway - TGF beta signaling pathway - MAPK/ERK pathway - Notch signaling pathway - JAK-STAT signaling pathway - cAMP dependent pathway - Akt/PKB signaling pathway - Fas apoptosis signaling pathway - Hippo signaling pathway - IP3/DAG pathway Agents Receptor ligands Hormones - Neurotransmitters - Cytokines - Growth factors Receptor Transmembrane - Intracellular Transcription factor General - Preinitiation complex - TFIID, TFIIH Other Adaptor protein - Scaffold protein

v • d • e Cell signaling: calcium signaling Second messengers IP3 - NAADP - cADPR Intracellular calcium store gates IP3 receptor - Ryanodine receptor - putative NAADP receptor Calcium pumps and exchangers SERCA - Na/Ca antiport - Ca/H antiport calcium-binding protein domains EF hand domain - C2 domain Calcium-based molecular switches, and kinases Troponin C - CaM - CaM kinases - PKC - NCS Intracellular calcium chelators (calcium buffers) and calcium sensors Calbindin - S100 - pervalbumin - Calretinin - Calsequestrin - Sarcalumenin - Phospholamban - Synaptotagmins Calcium-dependent proteases Calpain Calcium-dependent cytoskeleton remodeling proteins Gelsolin Cell membrane calcium channels VDCC - TRP - NMDA receptor - AMPA receptor - 5-HT3 receptor - P2X Receptor Calcium-regulated chaperones calreticulin - calnexin Calcium-based adhesion molecules Cadherin Calcium homeostasis Parathyroid hormone - Calcitonin - calcium receptor - vitamin D