Calcium concentration microdomains

Calcium concentration microdomains (CCMs) are sites in a cell's cytoplasm with a localised high calcium ion (Ca2+) concentration.[1] They are found immediately around the intracellular opening of calcium channels; when a calcium channel opens, the Ca2+ concentration in the adjacent CCM increases up to several hundred micromolar (µM).[2] These microdomains take part in calcium signaling, which has a diverse range of potential outcomes.[3]

Calcium concentration microdomains can be visualised with fluorescence microscopy by using aequorin as a reporter protein.[4]

Ion Channel Process

The actions of the Na-K-ATPase enzyme relate with the creation of calcium-signaling microdomains.[5] Na-K-ATPase is a protein that pumps Na+ and K+ across the cell membrane. Na-K-ATPase helps to keep the body at equilibrium by the movement of those ions through the plasma membrane. This ion pump helps to reset the movement of ions during an action potential by sending K+ into the cell and sending Na+ out of the cell. Since it opposes the normal flow of ions during an action potential, energy in the form of ATP (adenosine triphosphate) is used. Calcium is also regulated using this Na-K-ATPase due to the enzyme's interactions with protein and non-protein molecules. The main interaction that keeps calcium regulated is the binding of Na-K-ATPase to inositol 1,4,5-trisphosphate (IP3). IP3 is a secondary messenger that helps to send neuronal signals through the body. The neuronal cells have the calcium-signaling microdomains in the cytoplasm right next to the pre- and post-synaptic calcium channels in the nerve cells. Figure 1 is an example of how Na-K-ATPase forms the calcium-signaling microdomain.

The astrocytes which are star-shaped glial cells in the central nervous system are the main cells with these calcium-signaling micro domains. In fact, a rigorous mathematical analysis in astrocytes has shown that localized inflow of Ca2+ remains localized, despite the diffusion of cytosolic Ca2+ and potential storage in the endoplasmic reticulum.[6]

A Na+/Ca2+ exchanger (NCX) is also involved in regulating the amount of calcium in cells. The NCX switches the intra- and extra-cellular amounts of Na+ and Ca2+. NCX works together with Na-K-ATPase to create calcium concentration microdomains in certain cells like astrocytes discussed above. Specific forms of Na-K-ATPase, the α2 or α3 isoforms, actually interact with the NCX in the formation of the calcium microdomains in astrocytes.

Footnotes

[7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21]

References

  1. ↑ Serulle, Y.; Sugimori, M.; Llinas, R. R. (30 January 2007). "Imaging synaptosomal calcium concentration microdomains and vesicle fusion by using total internal reflection fluorescent microscopy". Proceedings of the National Academy of Sciences. 104 (5): 1697–1702. doi:10.1073/pnas.0610741104.
  2. ↑ Llinas, R; Sugimori, M; Silver, R. (1 May 1992). "Microdomains of high calcium concentration in a presynaptic terminal". Science. 256 (5057): 677–679. doi:10.1126/science.1350109. PMID 1350109.
  3. ↑ Demuro, A; Parker, I (Nov–Dec 2006). "Imaging single-channel calcium microdomains". Cell Calcium. 40 (5–6): 413–22. doi:10.1016/j.ceca.2006.08.006. PMC 1694561Freely accessible. PMID 17067668.
  4. ↑ Montero M, Brini M, Marsault R, Alvarez J, Sitia R, Pozzan T, Rizzuto R (1995). "Monitoring dynamic changes in free Ca2+ concentration in the endoplasmic reticulum of intact cells". EMBO J. 14 (22): 5467–75. PMC 394660Freely accessible. PMID 8521803.
  5. ↑ Tian, J.; Xie, Z. J. (August 2007). "The Na-K-ATPase and calcium-signaling microdomains". Physiology. 23 (4): 205–211. doi:10.1152/physiol.00008.2008.
  6. ↑ Lopez-Caamal, F.; Oyarzun, D.A.; Middleton, R.H.; Garcia, M.R. (May 2014). "Spatial Quantification of Cytosolic Ca2+ Accumulation in Nonexcitable Cells:An Analytical Study". IEEE/ACM Transactions on Computational Biology and Bioinformatics. 11 (3): 592–603. doi:10.1109/TCBB.2014.2316010.
  7. ↑ Axelrod, D. (2008). Total Internal Reflection Fluorescence Microscopy. In J. J. Correia & H. W. Detrich (Eds.), Biophysical Tools for Biologists, Vol 2: In Vivo Techniques (Vol. 89, pp. 169-221).
  8. ↑ Bunik, V., Kaehne, T., Degtyarev, D., Shcherbakova, T., & Reiser, G. (2008). Novel isoenzyme of 2-oxoglutarate dehydrogenase is identified in brain, but not in heart. Febs Journal, 275(20), 4990-5006. doi:10.1111/j.1742-4658.2008.06632.x
  9. ↑ Castillo, K., Bacigalupo, J., & Restrepo, D. (2008). Calcium Microdomains in the Chemosensory Cilia of Olfactory Receptor Neurons. Chemical Senses, 33(8), S61-S61.
  10. ↑ Clark, A. J. (2008). Observation of calcium microdomains at the uropod of living morphologically polarized human neutrophils using flash lamp-based fluorescence microscopy. Cytometry Part A, 73A(7), 673-678.
  11. ↑ Francis, A. A., Mehta, B., & Zenisek, D. (2011). Development of new peptide-based tools for studying synaptic ribbon function. Journal of Neurophysiology, 106(2), 1028-1037. doi:10.1152/jn.00255.2011
  12. ↑ Higgins, E. R. R. (2007). Modelling calcium microdomains using homogenisation. Journal of theoretical biology, 247(4), 623-644.
  13. ↑ Ibarretxe, G., Perrais, D., Jaskolski, F., Vimeney, A., & Mulle, C. (2007). Fast regulation of axonal growth cone motility by electrical activity. Journal of Neuroscience, 27(29), 7684-7695. doi:10.1523/jneurosci.1070-07.2007
  14. ↑ Lisman, J. E., Raghavachari, S., & Tsien, R. W. (2007). The sequence of events that underlie quantal transmission at central glutamatergic synapses. Nature Reviews Neuroscience, 8(8), 597-609. doi:10.1038/nrn2191
  15. ↑ Marchaland, J., Cali, C., Voglmaier, S. M., Li, H., Regazzi, R., Edwards, R. H., & Bezzi, P. (2009). CALCIUM MICRODOMAINS CONTROL EXO-ENDOCYTOSIS OF SYNAPTIC-LIKE MICROVESICLES IN ASTROCYTES. Glia, 57(13), S45-S45.
  16. ↑ Petibois, C., & Desbat, B. (2010). Clinical application of FTIR imaging: new reasons for hope. Trends in Biotechnology, 28(10), 495-500. doi:10.1016/j.tibtech.2010.07.003
  17. ↑ Ravier, M. A., Cheng-Xue, R., Palmer, A. E., Henquin, J. C., & Gilon, P. (2010). Subplasmalemmal Ca(2+) measurements in mouse pancreatic beta cells support the existence of an amplifying effect of glucose on insulin secretion. Diabetologia, 53(9), 1947-1957. doi:10.1007/s00125-010-1775-z
  18. ↑ Ravier, M. A., Tsuboi, T., & Rutter, G. A. (2008). Imaging a target of Ca(2+) signalling: Dense core granule exocytosis viewed by total internal reflection fluorescence microscopy. Methods, 46(3), 233-238. doi:10.1016/j.ymeth.2008.09.016
  19. ↑ Shigetomi, E., Kracun, S., & Khakh, B. S. (2010). Monitoring astrocyte calcium microdomains with improved membrane targeted GCaMP reporters. Neuron Glia Biology, 6(3), 183-191. doi:10.1017/s1740925x10000219
  20. ↑ Thomsen, L. B. T. L. B., Jorntell, H., & Midtgaard, J. (2010). Presynaptic calcium signalling in cerebellar mossy fibres. Frontiers in Neural Circuits, 4. doi:10.3389/neuro.04.001.2010
  21. ↑ Zhang, C. F., Liu, F. C., Liu, X. B., & Chen, D. J. (2010). Protective effect of N-acetylcysteine against BDE-209-induced neurotoxicity in primary cultured neonatal rat hippocampal neurons in vitro. International Journal of Developmental Neuroscience, 28(6), 521-528. doi:10.1016/j.ijdevneu.2010.05.003
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