Potentiation of GABA-mediated currents by cAMP-dependent protein kinase

Recent reports described a down-regulation of gamma-aminobutyric acid (GABA)-receptor function in several types of central neurones by cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA). Surprisingly, we found that in cerebellar Purkinje cells (PCs) the membrane permeable-compound 8-bromo-cAMP (500 microM) induced a long-lasting potentiation of both, whole-cell current responses to bath-applied GABA and amplitudes of miniature inhibitory synaptic currents (mIPSCs). When dialyzing the PCs with the specific protein kinase inhibitor peptide (PKIP, 400 micrograms ml-1), the same manipulation failed to induce a potentiation. These results strongly suggest that, in contrast to its action in other types of neurones, activation of PKA up-regulates the GABAA receptor function in cerebellar PCs.