Modification of GABA_A receptor function by an analog of cyclic AMP

Chloride-dependent current responses to γ-aminobutyric acid (GABA) were recorded from cultured rat hippocampal neurons under voltage clamp. In the presence of the membrane-permeable cyclic AMP analog, 8-bromo-cyclic AMP (8-Br-cAMP), the peak current response to GABA was reduced, although the reversal potential for the current evoked by GABA was unaltered; similar concentrations of 8-bromo-cyclic GMP did not alter the GABA response. 8-Br-cAMP also increased spontaneous activity of the neurons and blocked accommodation of firing. It is possible that the alterations in responses to GABA result from the activation of cyclic AMP-dependent protein kinase (cAMP-PK) and subsequent phosphorylation of the GABA_A receptor.