The role of intracellular Ca2+ stores in the control of brain activity was investigated in microdialysis experiments by monitoring changes in the extracellular concentration of amino acids (AA) in the hippocampus of the rat after intracerebroventricular (icv) administration of the intracellular Ca2+ release blocker, dantrolene in vivo, as well as in D-aspartate release and transmembrane Ca2+ flux measurements in dantrolene-treated (50 μM) hippocampal homogenates containing resealed plasmalemma fragments and nerve endings in vitro. Microdialysis data demonstrate that icv injection of 0.6 mM dantrolene significantly decreases (~20%) the background (Glu) in the hippocampus. Both the (Glu; ~300%) and the inhibitory effect of dantrolene thereupon (~50%) was significantly increased when 0.5 mM of the Glu uptake inhibitor, L-trans-pyrrolidine-2,4-dicarboxylic acid, was dialysed into the hippocampus. NMDA and (S)AMPA induced [3H]-D-aspartate release in hippocampal homogenates. Preincubation of these homogenates with 50 μM dantrolene was found to reduce the response to NMDA, but not to (S)-AMPA, in a NMDA-dependent manner. Increased rates of transmembrane influx and efflux of Ca2+ in hippocampal homogenates with halftimes of 4 ms and 200 ms, respectively, can be observed by the addition of 100 μM NMDA as recorded using a stopped-flow UV/fluorescence spectrometer in combination with the Ca2+ indicator dye, bisfura-2. Both the Ca2+ influx and efflux rates of the NMDA response were reduced (25-fold and >5-fold, respectively) in homogenates preloaded with 50 μM dantrolene. These results suggest a role for NMDA-inducible intracellular Ca2+ stores in the control of normal brain activity in vivo.
|Number of pages||10|
|Journal||Journal of Neuroscience Research|
|Publication status||Published - szept. 15 1999|
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience