The research program is focused on the structural and functional properties of ligand-gated channels in glia, with particular emphasis on glutamate-gated channels. Cell cultures of oligodendrocyte progenitors, in particular a primary cell line of progenitors (CG-4), served as an experimental model. These cells were found to express only kainate/AMPA receptor channels with a unique combination of subunits. Northern blot analysis with specific cDNA probes revealed the selective expression of only some of the members of the GluR-1-4, GluR-5-7 and KA-1-2 gene families. GluR-6, KA-1 and KA-2 were expressed at high levels, indicating that high-affinity kainate receptors are expressed in CG-4 cells. Patch-clamp recordings were obtained both on progenitors and in oligodendrocytes. In progenitor cells, concentration jump applications of L-glutamate, kainate and AMPA evoked large inward currents which rapidly desensitized. The kinetics of the onset of desensitization were similar for all three agonists. The steady-state response to kainate was on average 6 times larger than to L-glutamate. The response to kainate exhibited much less desensitization in pre-committed oligodendrocytes (O4-positive) and almost no desensitization in differentiated oligodendrocytes, indicating a developmental change in the expression of kainate/AMPA receptor subunits. Fura-2 fluorescence measurements indicated that the activation of kainate/AMPA receptors in CG-4 cells induced rapid changes in intracellular calcium both in progenitor cells and in precommitted oligodendrocytes. The receptor antagonist CNQX blocked the effects of kainate and glutamate.
| Gallo, V; Ghiani, C A (2000) Glutamate receptors in glia: new cells, new inputs and new functions. Trends Pharmacol Sci 21:252-8 |
| Ghiani, C A; Yuan, X; Eisen, A M et al. (1999) Voltage-activated K+ channels and membrane depolarization regulate accumulation of the cyclin-dependent kinase inhibitors p27(Kip1) and p21(CIP1) in glial progenitor cells. J Neurosci 19:5380-92 |
