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 5β-pregnan-3α-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.