Metabotropic glutamate receptor activation induces astroglial swelling.
The activation of metabotropic glutamate receptors (mGluRs) by 1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) or ibotenate induced a rapid cell volume increase in primary cultures of type 1 astroglial cells from the cerebral cortex of a newborn rat. These relative volume changes and parallel Ca2+ transients in single cells were examined by microspectrofluorimetry after loading the cells with fura-2/AM and varying the excitation wavelengths between the isosbestic point of the probe and its ion-sensitive wavelength. L(+)-2-Amino-4-phosphonobutyric acid (L-AP4) evoked an astroglial swelling but few or no cytosolic Ca2+ transients. No rapid swelling was observed after stimulation of ionotropic Glu receptors. The Glu-induced volume increase was unaffected by gluconate or amiloride, partially blocked by Glu-carrier blockers, and totally blocked by ketamine. The Glu- or L-AP4-induced volume increases were blocked by BaCl2 or furosemide. Tetraethylammoniumchloride-1-hydrate blocked the Glu- and 1S,3R-ACPD-induced astroglial swelling but the voltage-dependent L-, N-, or T-type Ca2+ channels were not primarily involved in the Glu-, 1S,3R-ACPD-, or L-AP4-induced swelling. mGluRs induce inositol 1,4,5-trisphosphate synthesis, intracellular Ca2+ increase, and the opening of a delayed outward K+ rectifier, and along another route they activate a Gi protein and open an inward K+ rectifier. One Na(+)-K(+)-2Cl(-)-cotransporter and a Na(+)-K(+)-ATPase is activated and so also is an electrogenic Na(+)-dependent Glu carrier. Thus, Glu-induced astroglial swelling is not only the result of the above mechanisms, but requires another, until now unidentified mechanism, probably some ketamine-sensitive K+ outflux or Na+ influx.
Hansson
E
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Institute of Neurobiology, University of Göteborg, Sweden.
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*
D005971:Glutamates; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D007051:Ibotenic Acid; D018698:Glutamic Acid; D002118:Calcium