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Chemical Compound Review

calcane     calcium(+2) cation

Synonyms: calcium ion, Calcium(2+), Calcium ions, Calcium (2+), Ca+2, ...
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Disease relevance of CALCIUM

  • At the tissue level, arrhythmia could be due to slowing of electrical spread after both Na(+) current decrease and cell-to-cell uncoupling as well as cell depolarization and Ca(2+) current increase [1].
  • Functional alterations of Ca(2+) handling seem to be responsible for the pathophysiological conditions seen in dystrophinopathies, Brody's disease, and malignant hyperthermia [2].
  • Deregulated Ca(2+) levels result in aberrant proteolysis by calpains, which contributes to tissue damage in heart and brain ischemias as well as neurodegeneration in Alzheimer's disease [3].
  • Inositol polyphosphate 5-phosphatases are central to intracellular processes ranging from membrane trafficking to Ca(2+) signaling, and defects in this activity result in the human disease Lowe syndrome [4].
  • Two distinct patterns of spontaneous Ca(2+) increases occurred in developing retinal ganglion cells--global increases throughout the arborization, and local 'flashes' of activity restricted to small dendritic segments [5].

Psychiatry related information on CALCIUM


High impact information on CALCIUM

  • Following engagement of the T cell receptor, intracellular channels (IP3 and ryanodine receptors) release Ca(2+) from intracellular stores, and by depleting the stores trigger prolonged Ca(2+) influx through store-operated Ca(2+) (CRAC) channels in the plasma membrane [11].
  • The amplitude and dynamics of the Ca(2+) signal are shaped by several mechanisms, including K(+) channels and membrane potential, slow modulation of the plasma membrane Ca(2+)-ATPase, and mitochondria that buffer Ca(2+) and prevent the inactivation of CRAC channels [11].
  • At short times, Ca(2+) signals help to stabilize contacts between T cells and antigen-presenting cells through changes in motility and cytoskeletal reorganization [11].
  • The complexity of Ca(2+) signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation [11].
  • Over periods of minutes to hours, the amplitude, duration, and kinetic signature of Ca(2+) signals increase the efficiency and specificity of gene activation events [11].

Chemical compound and disease context of CALCIUM


Biological context of CALCIUM

  • Highly enriched in brain tissue and present throughout the body, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is central to the coordination and execution of Ca(2+) signal transduction [17].
  • The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney [18].
  • Tm position on the actin filament is regulated by the occupancy of NH-terminal Ca(2+) binding sites on TnC, conformational changes resulting from Ca(2+) binding, and changes in the interactions among Tn, Tm, and actin and as well as by strong S1 binding to actin [19].
  • In different regions of the heart, action potential waveforms are distinct, owing to differences in Na(+), Ca(2+), and K(+) channel expression, and these differences contribute to the normal, unidirectional propagation of activity and to the generation of normal cardiac rhythms [20].
  • There is increasing evidence that the second messenger responsible for the modulation of the transduction cascade during background adaptation is primarily, if not exclusively, Ca(2+), whose intracellular free concentration is decreased by illumination [21].

Anatomical context of CALCIUM

  • Elevation of intracellular free Ca(2+) is one of the key triggering signals for T-cell activation by antigen [11].
  • Examples are ankyrin-dependent targeting of proteins to excitable membrane domains in the plasma membrane and the Ca(2+) homeostasis compartment of the endoplasmic reticulum [22].
  • Ca(2+) regulation of contraction in vertebrate striated muscle is exerted primarily through effects on the thin filament, which regulate strong cross-bridge binding to actin [19].
  • All muscle fibers use Ca(2+) as their main regulatory and signaling molecule [2].
  • In others, localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+) [18].

Associations of CALCIUM with other chemical compounds


Gene context of CALCIUM

  • Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow [27].
  • Injection of wildtype and mutated FZD4 into Xenopus laevis embryos revealed that wildtype, but not mutant, frizzled-4 activated calcium/calmodulin-dependent protein kinase II (CAMKII) and protein kinase C (PKC), components of the Wnt/Ca(2+) signaling pathway [28].
  • The most extensively studied candidate for the Ca(2+)-sensing trigger is synaptotagmin I, whose Ca(2+)-dependent interactions with acidic phospholipids and syntaxin have largely been ascribed to its C(2)A domain, although the C(2)B domain also binds Ca(2+) (refs 7, 8) [29].
  • Here we identify PKC-alpha as a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes [30].
  • P2rx4(-/-) mice do not have normal endothelial cell responses to flow, such as influx of Ca(2+) and subsequent production of the potent vasodilator nitric oxide (NO) [31].

Analytical, diagnostic and therapeutic context of CALCIUM

  • Increased perfusion pressure increases microvascular volume, thereby opening stretch-activated ion channels, resulting in an increased intracellular Ca(2+) transient, which is followed by an increase in Ca(2+) sensitivity and higher muscle contractility (Gregg effect) [32].
  • Electrophysiological studies have detailed the properties of the Na(+), Ca(2+), and K(+) currents that generate cardiac action potentials, and molecular cloning has revealed a large number of pore forming (alpha) and accessory (beta, delta, and gamma) subunits thought to contribute to the formation of these channels [20].
  • Each of the mutant proteins has a dramatically reduced affinity for Ca2+; one does not bind detectable levels of 45Ca2+ either during gel filtration or when bound to a solid support [33].
  • Using combined two-photon laser scanning microscopy and two-photon laser uncaging of glutamate, we show that SK channels regulate NMDAR-dependent Ca(2+) influx within individual spines [34].
  • To elucidate this neuronal circuit at the molecular level, we established a functional OR identification strategy based on glomerular activity by combining in vivo Ca(2+) imaging, retrograde dye labeling, and single-cell RT-PCR [35].


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  3. A Ca(2+) switch aligns the active site of calpain. Moldoveanu, T., Hosfield, C.M., Lim, D., Elce, J.S., Jia, Z., Davies, P.L. Cell (2002) [Pubmed]
  4. Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase. Tsujishita, Y., Guo, S., Stolz, L.E., York, J.D., Hurley, J.H. Cell (2001) [Pubmed]
  5. Transmitter-evoked local calcium release stabilizes developing dendrites. Lohmann, C., Myhr, K.L., Wong, R.O. Nature (2002) [Pubmed]
  6. Neuronal substrates of complex behaviors in C. elegans. de Bono, M., Maricq, A.V. Annu. Rev. Neurosci. (2005) [Pubmed]
  7. Calcium activation of heart mitochondrial oxidative phosphorylation: rapid kinetics of mVO2, NADH, AND light scattering. Territo, P.R., French, S.A., Dunleavy, M.C., Evans, F.J., Balaban, R.S. J. Biol. Chem. (2001) [Pubmed]
  8. RhoA-mediated Ca2+ sensitization in erectile function. Wang, H., Eto, M., Steers, W.D., Somlyo, A.P., Somlyo, A.V. J. Biol. Chem. (2002) [Pubmed]
  9. Association analysis of G-protein beta 3 subunit gene with altered Ca(2+) homeostasis in bipolar disorder. Corson, T.W., Li, P.P., Kennedy, J.L., Macciardi, F., Cooke, R.G., Parikh, S.V., Warsh, J.J. Mol. Psychiatry (2001) [Pubmed]
  10. Differential changes in alpha- and beta-adrenoceptor linked [45Ca2+] uptake in platelets from patients with anorexia nervosa. Gill, J., DeSouza, V., Wakeling, A., Dandona, P., Jeremy, J.Y. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  11. Calcium signaling mechanisms in T lymphocytes. Lewis, R.S. Annu. Rev. Immunol. (2001) [Pubmed]
  12. Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development. Kurth, I., Willimann, K., Schaerli, P., Hunziker, T., Clark-Lewis, I., Moser, B. J. Exp. Med. (2001) [Pubmed]
  13. Expression of Ca(2+)-permeable AMPA receptor channels primes cell death in transient forebrain ischemia. Liu, S., Lau, L., Wei, J., Zhu, D., Zou, S., Sun, H.S., Fu, Y., Liu, F., Lu, Y. Neuron (2004) [Pubmed]
  14. Examining the role of mitochondrial respiration in vanilloid-induced apoptosis. Hail, N., Lotan, R. J. Natl. Cancer Inst. (2002) [Pubmed]
  15. A novel claudin 16 mutation associated with childhood hypercalciuria abolishes binding to ZO-1 and results in lysosomal mistargeting. Müller, D., Kausalya, P.J., Claverie-Martin, F., Meij, I.C., Eggert, P., Garcia-Nieto, V., Hunziker, W. Am. J. Hum. Genet. (2003) [Pubmed]
  16. Paclitaxel induces calcium oscillations via an inositol 1,4,5-trisphosphate receptor and neuronal calcium sensor 1-dependent mechanism. Boehmerle, W., Splittgerber, U., Lazarus, M.B., McKenzie, K.M., Johnston, D.G., Austin, D.J., Ehrlich, B.E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and autoregulation in cellular function. Hudmon, A., Schulman, H. Annu. Rev. Biochem. (2002) [Pubmed]
  18. Extracellular calcium sensing and extracellular calcium signaling. Brown, E.M., MacLeod, R.J. Physiol. Rev. (2001) [Pubmed]
  19. Regulation of contraction in striated muscle. Gordon, A.M., Homsher, E., Regnier, M. Physiol. Rev. (2000) [Pubmed]
  20. Molecular physiology of cardiac repolarization. Nerbonne, J.M., Kass, R.S. Physiol. Rev. (2005) [Pubmed]
  21. Adaptation in vertebrate photoreceptors. Fain, G.L., Matthews, H.R., Cornwall, M.C., Koutalos, Y. Physiol. Rev. (2001) [Pubmed]
  22. Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. Bennett, V., Baines, A.J. Physiol. Rev. (2001) [Pubmed]
  23. Ischemic cell death in brain neurons. Lipton, P. Physiol. Rev. (1999) [Pubmed]
  24. NAADP mobilizes Ca(2+) from reserve granules, lysosome-related organelles, in sea urchin eggs. Churchill, G.C., Okada, Y., Thomas, J.M., Genazzani, A.A., Patel, S., Galione, A. Cell (2002) [Pubmed]
  25. S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide. Adachi, T., Weisbrod, R.M., Pimentel, D.R., Ying, J., Sharov, V.S., Schöneich, C., Cohen, R.A. Nat. Med. (2004) [Pubmed]
  26. Spatiotemporal dynamics of inositol 1,4,5-trisphosphate that underlies complex Ca2+ mobilization patterns. Hirose, K., Kadowaki, S., Tanabe, M., Takeshima, H., Iino, M. Science (1999) [Pubmed]
  27. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nauli, S.M., Alenghat, F.J., Luo, Y., Williams, E., Vassilev, P., Li, X., Elia, A.E., Lu, W., Brown, E.M., Quinn, S.J., Ingber, D.E., Zhou, J. Nat. Genet. (2003) [Pubmed]
  28. Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy. Robitaille, J., MacDonald, M.L., Kaykas, A., Sheldahl, L.C., Zeisler, J., Dubé, M.P., Zhang, L.H., Singaraja, R.R., Guernsey, D.L., Zheng, B., Siebert, L.F., Hoskin-Mott, A., Trese, M.T., Pimstone, S.N., Shastry, B.S., Moon, R.T., Hayden, M.R., Goldberg, Y.P., Samuels, M.E. Nat. Genet. (2002) [Pubmed]
  29. Synaptotagmins I and IV promote transmitter release independently of Ca(2+) binding in the C(2)A domain. Robinson, I.M., Ranjan, R., Schwarz, T.L. Nature (2002) [Pubmed]
  30. PKC-alpha regulates cardiac contractility and propensity toward heart failure. Braz, J.C., Gregory, K., Pathak, A., Zhao, W., Sahin, B., Klevitsky, R., Kimball, T.F., Lorenz, J.N., Nairn, A.C., Liggett, S.B., Bodi, I., Wang, S., Schwartz, A., Lakatta, E.G., DePaoli-Roach, A.A., Robbins, J., Hewett, T.E., Bibb, J.A., Westfall, M.V., Kranias, E.G., Molkentin, J.D. Nat. Med. (2004) [Pubmed]
  31. Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Yamamoto, K., Sokabe, T., Matsumoto, T., Yoshimura, K., Shibata, M., Ohura, N., Fukuda, T., Sato, T., Sekine, K., Kato, S., Isshiki, M., Fujita, T., Kobayashi, M., Kawamura, K., Masuda, H., Kamiya, A., Ando, J. Nat. Med. (2006) [Pubmed]
  32. Cross-talk between cardiac muscle and coronary vasculature. Westerhof, N., Boer, C., Lamberts, R.R., Sipkema, P. Physiol. Rev. (2006) [Pubmed]
  33. Can calmodulin function without binding calcium? Geiser, J.R., van Tuinen, D., Brockerhoff, S.E., Neff, M.M., Davis, T.N. Cell (1991) [Pubmed]
  34. SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines. Ngo-Anh, T.J., Bloodgood, B.L., Lin, M., Sabatini, B.L., Maylie, J., Adelman, J.P. Nat. Neurosci. (2005) [Pubmed]
  35. Odorant receptor map in the mouse olfactory bulb: in vivo sensitivity and specificity of receptor-defined glomeruli. Oka, Y., Katada, S., Omura, M., Suwa, M., Yoshihara, Y., Touhara, K. Neuron (2006) [Pubmed]
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