Modification of GABAA receptor function by an analog of cyclic AMP.
Chloride-dependent current responses to gamma-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 GABAA receptor.
Harrison
N L
NL
Laboratory of Neurophysiology, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Lambert
N A
NA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*
D002712:Chlorides; D007473:Ion Channels; D011963:Receptors, GABA-A; D015124:8-Bromo Cyclic Adenosine Monophosphate