Role of Intracellular Calcium Stores on the Effect of Metabotropic Glutamate Receptors on Phosphorylation of Glial Fibrillary Acidic Protein in Hippocampal Slices from Immature Rats

Abstract

Phosphorylation of glial fibrillary acidic protein (GFAP) in slices from immature rats is stimulated by glutamate via a group II metabotropic glutamate receptor (mGluR II) and by absence of external Ca²⁺ in reactions that are not additive (Wofchuk and Rodnight, Neurochem. Int. 24:517–523, 1994). These observations suggested that glutamate, via an mGluR, inhibits Ca²⁺-entry through L-type Ca²⁺ channels and down-regulates a Ca²⁺-dependent dephosphorylation event coupled to GFAP. Because ryanodine receptors are present on internal Ca²⁺ stores and are associated with L-type Ca²⁺-channels, we investigated the possibility that the glutamatergic modulation of GFAP phosphorylation involves internal Ca²⁺ stores regulated by ryanodine receptors and whether the Ca²⁺ originating from these stores acts in a similar manner to external Ca²⁺. The results showed that the ryanodine receptor–agonists, caffeine and ryanodine and thapsigargin, all of which in appropriate doses increase cytoplasmic Ca²⁺, reversed the stimulation of GFAP phosphorylation given by 1S,3R-ACPD, an mGluR II agonist.