Developmental profile of excitatory GABA(A) responses in cultured rat cerebellar granule cells.
GABA induced a transient increase in cytosolic free Ca2+ in cerebellar granule cells, which decreased from 3 to 8 days in vitro (DIV). Cytosolic Ca2+ changes induced by glutamate/glycine were comparable at 3 and 7 DIV. The GABA response was ascribed to GABA(A)-receptor mediated depolarization activating L-type Ca2+ channels since the response was inhibited by bicuculline or nifedipine. GABA-mediated Ca2+ rise at 4 DIV was potentiated by pentobarbital or by the neurosteroid 5beta-pregnan-3alpha-ol-20-one, or by decreasing the extracellular Cl- concentration. Neurons cultured for > 7 DIV showed no rise in intracellular Ca2+ in response to GABA regardless of the Cl- gradient. GABA(A) receptor-mediated cytosolic Ca2+ rise suggests an important role for the excitatory activity of GABA in developing cerebellar granule neurons.
Department of Pharmacology and Neuroscience, Ninewells Medical School, University of Dundee, UK.
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Rego
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Lambert
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Nicholls
D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002712:Chlorides; D018756:GABA Antagonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D013256:Steroids; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital; D009543:Nifedipine; D002118:Calcium; D001640:Bicuculline