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Primary culture of oligodendrocyte-progenitor cells from rat brain: electrophysiological properties and effect of ischemic factors.

By Roeland Buckinx 

Recent research has shown that there can be a hypoxic (shortage of oxygen) and/or an ischemic  (too low blood flow) component in Multiple Sclerosis [1,2]. The cell that is primarily affected in MS is the oligodendrocyte, which is very important for a proper conduction of signals in the central nervous system.  Since this cell type plays such a big role, its functional recovery is important in recovery during MS.  The cells that develop into mature oligodendrocytes are called progenitor cells, and the presence and health of these cells may be crucial for recovery of the oligodendrocyte population when affected by MS. Unfortunately, these progenitor cells are also very sensitive to ischemia. [3-5] Given this background information, we want to look at the influences of ischemic factors on the progenitor cells of oligodendrocytes. A couple of these ischemic factors are a rise in calcium-concentration in the cell, a drop in the amount of intracellular ATP (a crucial molecule in the bioenergetics of cells), a local acidification and a local shortage of oxygen. We especially focus on the electrofysiological changes in these cells. We examine the ion currents through the membrane of these cells. The ion currents that pass through a cell membrane are very important for the ion homeostasis of the cellular cytosol.

 

We can measure these current with the help of the “whole cell” patch clamp technique, for which the basic technique was developed by Erwin Neher and Bert Sakmann. For this achievement they were awarded the Nobel Price in Medicine in 1991 (http://www.nobel.se/medicine/laureates/1991/). When using the “whole cell” variant of this technique we place a very small glass pipette on the cell membrane, and cause a small negative pressure in the pipette, which eventually breaks the membrane locally (fig. 1). This procedure allows to get access to the inside of the cell and to dialyse its interior. The patch clamp technique allows the researcher to clamp the membrane voltage to a certain value, using an appropriate electrical circuit. In this way, we can measure and study the ion currents that cross the membrane in function of the applied membrane potential. We intend to study how the above mentioned ischemic factors might affect the different ion currents.

Research funded by a Ph.D. grant of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT Vlaanderen). 

  1. Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., and Lassmann, H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47: 707-17, 2000.

  2. Lassmann, H. Hypoxia-like tissue injury as a component of multiple sclerosis lesions. J Neurol Sci 206: 187-91, 2003.

  3. Blakemore, W. F. and Keirstead, H. S. The origin of remyelinating cells in the central nervous system. J Neuroimmunol 98: 69-76, 1999.

  4. Levine, J. M. , Reynolds, R., and Fawcett, J. W. The oligodendrocyte precursor cell in health and disease. Trends Neurosci 24: 39-47, 2001.

  5. Paz Soldan, M. M. and Rodriguez, M. Heterogeneity of pathogenesis in multiple sclerosis: implications for promotion of remyelination. J Infect Dis 186 Suppl 2: S248-53, 2002.

 



 
 

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