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.
Kano
M
M
Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Konnerth
A
A
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D010455:Peptides; D047428:Protein Kinase Inhibitors; C061479:protein kinase inhibitor peptide; D015124:8-Bromo Cyclic Adenosine Monophosphate; D005680:gamma-Aminobutyric Acid; D011494:Protein Kinases