Cyclic AMP-dependent protein kinase decreases GABAA receptor current in mouse spinal neurons

Nada M. Porter, Roy E. Twyman, Michael D. Uhler, Robert L. Macdonald

Research output: Contribution to journalArticlepeer-review

175 Scopus citations


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.

Original languageEnglish
Pages (from-to)789-796
Number of pages8
Issue number6
StatePublished - Dec 1990

Bibliographical note

Funding Information:
We thank Dr. Carl J. Rogers for writing the single-channel detection program and for computer hardware and software implementation. We also thank Ms. Nancy E. Ciliax for maintaining cultures and for illustrations. This work was supported by an individual NRSA postdoctoral fellowship to N. M. P. (NSB8216), by an American Academy of Neurology and Neuropharmacology Fellowship and a CIDA award (NS01266) to R. E. T., by USPHS grants to M. D. U. (CM38788) and R. L. M. (NS19613), and by a grant from the Lucille P. Markey Charitable Trust.

ASJC Scopus subject areas

  • General Neuroscience


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