Trends in Neurosciences
News on glutamate receptors in glial cells
Section snippets
Molecular biology and functional properties of glutamate receptors
Based on their pharmacological and electrophysiological properties, iGlu receptors have been subdivided into three subtypes: AMPA, kainate and NMDA receptors. These receptors contain integral cationic ion channels that are associated with the ligand binding site. Unlike iGlu receptors, mGlu receptors are coupled to G proteins regulating either inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-mediated release of intracellular Ca2+, or inhibition of intracellular cAMP production. Molecular cloning and
Physiological properties of ionotropic glutamate receptors
A variety of native iGlu receptors and mGlu receptors have been characterized in glia in situ or in freshly isolated cells (Table 1). Glial cells in the corpus callosum24, 25, Bergmann glial cells in the cerebellum[26], and astrocytes in the hippocampus28, 29, 30, 31, 33express receptors with functional and pharmacological properties of the AMPA subtype. These in situ studies have shown that glutamate and kainate not only activated a cationic receptor conductance, but also significantly reduced
Properties of glial glutamate receptors in vitro
The functional properties of iGlu receptors and mGlu receptors have been analysed in different glial cell types in vitro. Expression of iGlu receptors has been consistently demonstrated in all macroglial cells, but mGlu receptors appear to be expressed only in astrocytes60, 61, 62, 63(however, see Ref. [64]). Molecular, electrophysiological and biophysical studies in cultured cells confirmed that glial and neuronal iGlu receptors are made up of the same subunits with similar functional
Concluding remarks
Millimolar concentrations of glutamate are released from axons and presynaptic terminals during and after the propagation of action potentials95, 96, 97. The cytoarchitectural arrangement of the two major macroglial cell types in the brain implies that neuronal glutamate-dependent signals can directly activate glial receptors. Astrocytes are in the position to sense synaptic activity at their processes that interdigitate with nerve endings. Oligodendrocytes, on the other hand, can respond to
Future directions
The complete understanding of the physiological role of Glu receptors in glia is most definitely a challenge for the future. It is still unclear whether these and other neurotransmitter receptors perform specific tasks in distinct macroglial cell types during CNS development and in the mature brain. The question of whether glial Glu receptors are indeed activated in situ during neural activity is also unanswered. If this is the case, are there specific patterns of activation that result in
Acknowledgements
CS acknowledges grants from the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, the Sandoz Foundation, and the Fonds der Chemischen Industrie. We thank Mario Pende for the data presented in Fig. 4, Klaus Kressin for assistance with Fig. 5, and Chris McBain and Mario Pende for critically reading the manuscript.
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