Glutamate-triggered calcium signalling in mouse bergmann glial cells in situ: role of inositol-1,4,5-trisphosphate-mediated intracellular calcium release.
The mechanisms of glutamate-induced changes in intracellular free calcium concentration in Bergmann glial cells in mouse cerebellar slices were investigated by Fura-2-based microfluorimetry. Extracellular applications of glutamate, quisqualate and kainate triggered an increase in cytoplasmic calcium concentration, whereas N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate were ineffective. The calcium elevation triggered by kainate was completely blocked by removal of calcium ions from the external solutions or by slice incubation with 6-cyano-7-nitroquinoxaline-2,3-dione. Conversely, both glutamate- and quisqualate-induced intracellular calcium transients were only slightly attenuated by slice incubation with either 6-cyano-7-nitroquinoxaline-2,3-dione or calcium-free solution, suggesting the intracellular origin for calcium ions. The glutamate-triggered cytosolic calcium increases were inhibited by slice incubation with thapsigargin, the inhibitor of intracellular calcium pumps, or by intracellular perfusion of Bergmann glial cells with heparin, the antagonist of inositol-1,4,5-trisphosphate-gated calcium release channels. Therefore the calcium release from inositol-1,4,5-trisphosphate-sensitive intracellular stores plays the major role in glutamate-induced calcium signalling. We concluded that Bergmann glial cells express calcium permeable ionotropic glutamate receptors, which might be important for generation of fast calcium signals. However, slow glutamate-evoked calcium signals are mostly determined by inositol-1,4,5-trisphosphate-dependent intracellular signalling chain.
Kirischuk
S
S
Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Kirchhoff
F
F
Matyash
V
V
Kettenmann
H
H
Verkhratsky
A
A
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology*
D000596:Amino Acids; D018698:Glutamic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium