Agonist-evoked Ca2+ transients in primary astroglial cultures--modulatory effects of valproic acid.
Cytosolic Ca2+ ([Ca2+]i) activity was measured in individual type 1 astroglial cells in primary culture after exposure to glutamate (Glu), quisqualate (QA), gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5HT), and noradrenaline (NA) by using the Ca2+ indicator dye fura-2/AM in a computerized microspectrofluorimetric system. Various patterns of Ca2+ transients were observed, but the most common was biphasic, having an initial sharp peak, rising immediately after stimulation, and then declining to a lower but sustained Ca2+ level. The only substance that diverged from this pattern was GABA, which induced a Ca2+ response with longer latency and a single-phase curve. The effects of the anticonvulsive drug Na(+)-valproate (VPA) were also investigated. After both acute and chronic (5-7 days) exposure to 10(-4) M VPA, the GABA-evoked rises in [Ca2+]i were completely inhibited. VPA also had acute effects on the 5HT- and Glu-evoked Ca2+ spikes. The Ca2+ responses after 5HT stimulation were greatly reduced after exposure to 10(-4) M VPA. The responses after glutamate stimulation were, on the contrary, increased after a similar exposure. No VPA effects were seen on the curve patterns of QA and NA stimulations. The most frequent agonist-evoked responses were seen after stimulation with 5HT and NA, where over 80% of the tested cells responded. For QA and Glu, the response frequencies were about 40% each, while for GABA it was 20%. The responses after 5HT and NA stimulation were blocked to baseline levels after exposure to ketanserin (5HT2 receptor antagonist) and a combination of prazosin, yohimbine, and propranolol (alpha 1, alpha 2, and beta adrenoceptor antagonists, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Nilsson
M
M
Institute of Neurobiology, University of Göteborg, Sweden.
Hansson
E
E
Rönnbăck
L
L
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D016257:Fura-2 / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013050:Spectrometry, Fluorescence; D014635:Valproic Acid / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D014635:Valproic Acid; D002118:Calcium; D016257:Fura-2