Detection of Intracellular Free Metal Ions with Molecular Two-Photon Sensors

이광자 분자센서를 이용한 생체 내 금속이온 검출

  • 김환명 (아주대학교 에너지시스템학부)
  • Received : 2011.07.18
  • Accepted : 2011.08.13
  • Published : 2011.09.30


Two-photon microscopy (TPM) is attracting much attention in biological imaging due to the capability of imaging deep inside the living tissues for a long period of time. For maximum utilization of TPM, it is essential to develop efficient twophoton sensors. Regarding this, many research groups are developing two-photon sensors for specific applications. In this review, we summarize recent results on selected examples of two-photon sensors for intracellular free metal ions in the live cells and tissues to provide a guideline for various imaging applications.


Supported by : 아주대학교, 한국연구재단


  1. Zipfel, W. R., Williams, R. M., and Webb, W. W., "Nonlinear Magic: Multiphoton Microscopy in the Biosciences," Nat. Bio technol., 21, 1369-1377 (2003).
  2. Helmchen, F., and Denk, W., "Deep Tissue Two-photon Microscopy," Nat. Methods, 2(12), 932-940 (2005).
  3. Williams, R. M., Zipfel, W. R., and Webb, W. W., "Multiphoton Microscopy in Biological Research," Curr. Opin. Chem. Biol., 5(5), 603-608 (2001).
  4. Xu, C., Zipfel, W., Shear, J. B., Williams, R. M., and Webb, W. W., "Multiphoton Fluorescence Excitation: New Spectral Windows for Biological Nonlinear Microscopy," Proc. Natl. Acad. Sci. USA, 93(20), 10763-10768 (1996).
  5. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P., "Molecular Biology of the Cell," 4th ed.; Taylor & Francis Group: New York (2002).
  6. Lippard, S. J., and Berg, J. M., "Principles of Bioinorganic Chemistry," University Science Books, Mill Valley, California, USA, (1994)
  7. Bae, M. A., Kwak, I. S., Won, S. W., and Yun, Y. S., "Gold Recovery from Cyanide Solution through Biosorption, Desorption, and Incineration with Waste Biomass of Corynebacterium Glutamicum as Biosorbent," Clean Technology, 16(2), 117-123 (2010).
  8. Kim, H. M., and Cho, B. R., "Two-photon Probes for Intracellular Free Metal Ions, Acidic Vesicles, and Lipid Rafts in Live Tissues," Acc. Chem. Res., 42(7), 863-872 (2009).
  9. Kim, H. M., and Cho, B. R., "Two-Photon Fluorescent Probes for Metal Ions," Chem.-Asian J., 6, 58-69 (2011).
  10. Rubin, H., "Magnesium: The Missing Element in Molecular Views of Cell Proliferation Control," BioEssays, 27(3), 311- 320 (2005).
  11. Eskes, R., Antonsson, B., Osen-Sand, A., Montessuit, S., Richter, C., Sadoul, R., Mazzei, G., Nichols, A., and Martinou, J. C., "Bax-induced Cytochrome C Release from Mitochondria is Independent of the Permeability Transition Pore but Highly Dependent on $Mg^{2+}$ Ions," J. Cell Biol., 143(1), 217-224 (1998).
  12. "Magnesium and the Cell"; Birch, N. J., Ed.; Academic Press: San Diego, CA (1993).
  13. Kim, H. M., Jung, C., Kim, B. R., Jung, S. Y., Hong, J. H., Ko, Y. G., Lee, K. J., and Cho, B. R., "Environment-sensitive Two-photon Probe for Intracellular Free Magnesium Ions in Live Tissue," Angew. Chem. Int. Ed, 46(19), 3460-3463 (2007).
  14. The Handbooks-A Guide to Fluorescent Probes and Labeling Technologies, 10th ed,; Haugland, R. P. Ed.; Molecular Probes: Eugene, OR (2005).
  15. Fitz, J. G., Sostman, A. H., and Middleton, J. P., "Regulation of Cation Channels in Liver Cells by Intracellular Calcium and Protein Kinase C," Am. J. Physiol. (London), 266(4), G677-G684 (1994)
  16. Cho, M. R., Thatte, H. S., Silvia, M. T., and Golan, D. E., "Transmembrane Calcium Influx Induced by ac Electric Fields," FASEB J., 13(6), 677-683 (1999).
  17. Berridge, M. J., Bootman, M. D., and Roderick, H. L., "Calcium Signalling: Dynamics, Homeostasis and Remodeling," Nat. Rev. Mol. Cell Biol., 4(7), 517-529 (2003).
  18. Orrenius, S., Zhivotovsky, B., and Nicotera, P., "Regulation of Cell Death: the Calcium-Apoptosis Link," Nat. Rev. Mol. Cell Biol., 4, 552-565 (2003).
  19. Rizzuto R., and Pozzan T., "Microdomains of Intracellular $Ca^{2+}$: Molecular Determinants and Functional Consequences," Physiol. Rev., 86(1), 369-408 (2006).
  20. Kim, H. M., Kim, B. R., Hong, J. H., Park, J. S., Lee, K. J., and Cho, B. R., "A Two-photon Fluorescent Probe for Calcium Waves in Living Tissue," Angew. Chem. Int. Ed., 46(39), 7445-7448 (2007).
  21. Kim, H. M., Kim, B. R., An, M. J., Hong, J. H., Lee, K. J., and Cho, B. R., "Two-photon Fluorescent Probes for Long-term Imaging of Calcium Waves in Live Tissue," Chem.Eur. J., 14(7), 2075-2083 (2008).
  22. Burnier, M., "Sodium in Health Disease," Informa Healthcare, M. Burnier, New York (2008).
  23. The$ Na^+$, $K^+$ Pump, Part B: Cellular Aspects, ed. J. C. Skou, J. G. Norby, A. B. Maunsbach, M. Esmann, Alan R. Liss, John Wiley & Sons, New York, USA (1998).
  24. Murphy, E., and Eisner, D. A., "Regulation of Intracellular and Mitochondrial Sodium in Health and Disease," Circ. Res., 104(3), 292-303 (2009).
  25. Kim, M. K., Lim, C. S., Hong, J. T., Han, J. H., Jang, H. Y., Kim, H. M., and Cho, B. R., "Sodium-ion-selective Twophoton Fluorescent Probe for in Vivo Imaging," Angew. Chem. Int. Ed., 49(2), 364-367 (2010).
  26. Scheiner-Bobis, G., and Schoner, W., "A Fresh Facet for Ouabain Action," Nat. Med., 7(11), 1288-1289 (2001).
  27. Chatton, J. Y., Marquet, P., and Magistretti, P. J., "A Quantitative Analysis of L-glutamate-regulated $Na^+$ Dynamics in Mouse Cortical Astrocytes: Implications for Cellular Bioenergetics," Eur. J. Neurosci., 12, 3843-3853 (2000).
  28. Blaustein, M. P., and Lederer, W. J., "Sodium/calcium Exchange: Its Physiological Implications," Physiol. Rev., 79(3), 763-854 (1999).
  29. Mohan, P. S., Lim, C. S., Tian, Y. S., Roh, W. Y., Lee, J. H., and Cho, B. R., "A Two-photon Fluorescent Probe for Near-membrane Calcium Ions in Live Cells and Tissues," Chem. Commun., 36, 5365-5367 (2009).
  30. Shin, Y. N., Lim, C. S., Tian, Y. S., No, W. Y., and Cho, B. R., "Detection of Near-membrane Calcium Ions in Live Tissues with Two-Photon Fluorescent Probes," Bull. Korean Chem. Soc., 31(3), 599-605 (2010).
  31. Kim, H. J., Han, J. H., Kim, M. K., Lim, C. S., Kim, H. M., and Cho, B. R., "Dual-Color Imaging of Sodium/Calcium Ion Activities with Two-Photon Fluorescent Probes," Angew. Chem. Int. Ed., 49(38), 6786-6789 (2010).
  32. Houchi, H., Kitamura, K., Minakuchi, K., Ishimura, Y., Okuno, M., Ohuchi, T., and Oka, M., "Mechanism of Histamineinduced Calcium Efflux from Cultured Bovine Adrenal Chromaffin Cells: Possible Involvement of an $Na^+$/$Ca^{2+}$ Exchange Mechanism," Neurosci. Lett., 180(2), 281-284 (1994).