title: Cyclic AMP-dependent protein kinase decreases GABAA receptor current in mouse spinal neurons.
abstract: GABA, the major inhibitory neurotransmitter in the mammalian brain, binds to GABAA receptors, which form chloride ion channels. The predicted structure of the GABAA receptor places a consensus phosphorylation site for cAMP-dependent protein kinase (PKA) on an intracellular domain of the channel. Phosphorylation by various protein kinases has been shown to alter the activity of certain ligand- and voltage-gated ion channels. We have examined the role of phosphorylation by the catalytic subunit of PKA in the regulation of GABAA receptor channel function using whole-cell and excised outside-out patch-clamp techniques. Inclusion of the catalytic subunit of PKA in the recording pipettes significantly reduced GABA-evoked whole-cell and single-channel chloride currents. Both heat inactivation of PKA and addition of the specific protein kinase inhibitor peptide prevented the reduction of GABA-evoked currents by PKA. Neither mean channel open time nor channel conductance was affected by PKA. The reduction in GABA receptor current by PKA was primarily due to a reduction in channel opening frequency.
authors.affiliation: Department of Neurology, University of Michigan Medical Center, Ann Arbor 48104.
authors.forename: N M
authors.initials: NM
authors.lastname: Porter
authors.forename: R E
authors.initials: RE
authors.lastname: Twyman
authors.forename: M D
authors.initials: MD
authors.lastname: Uhler
authors.forename: R L
authors.initials: RL
authors.lastname: Macdonald
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D018118:Chloride Channels; D000242:Cyclic AMP / Q000494:pharmacology*; D004553:Electric Conductivity; D006358:Hot Temperature; D015640:Ion Channel Gating / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D008565:Membrane Proteins; D010455:Peptides; D047428:Protein Kinase Inhibitors; D011963:Receptors, GABA-A; C061479:protein kinase inhibitor peptide; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D000242:Cyclic AMP; D011494:Protein Kinases