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The Journal of Neuroscience, January 15, 1999, 19(2):674-683
Modulation of Synaptic GABAA Receptor Function by PKA
and PKC in Adult Hippocampal Neurons
Pierrick
Poisbeau2,
Michael C.
Cheney1,
Michael
D.
Browning3, and
Istvan
Mody1
1 Departments of Neurology and Physiology, University
of California at Los Angeles, School of Medicine, Los Angeles,
California 90095, 2 Laboratoire de Neurophysiologie
Cellulaire et Intégrée, Centre National de la Recherche
Scientifique UMR 7519, Université Louis Pasteur, 67084 Strasbourg, France, and 3 Department of
Pharmacology, University of Colorado Health Science Center, Denver,
Colorado 80262
Several protein kinases are known to phosphorylate Ser/Thr residues
of certain GABAA receptor subunits. Yet, the effect of phosphorylation on GABAA receptor function in neurons
remains controversial, and the functional consequences of
phosphorylating synaptic GABAA receptors of adult CNS
neurons are poorly understood. We used whole-cell patch-clamp
recordings of GABAA receptor-mediated miniature IPSCs
(mIPSCs) in CA1 pyramidal neurons and dentate gyrus granule cells (GCs)
of adult rat hippocampal slices to determine the effects of
cAMP-dependent protein kinase (PKA) and
Ca2+/phospholipiddependent protein kinase (PKC)
activation on the function of synaptic GABAA receptors. The
mIPSCs recorded in CA1 pyramidal cells and in GCs were differentially
affected by PKA and PKC. In pyramidal cells, PKA reduced mIPSC
amplitudes and enhanced the fraction of events decaying with a double
exponential, whereas PKC was without effect. In contrast, in GCs
PKA was ineffective, but PKC increased the peak amplitude of
mIPSCs and also favored double exponential decays. Intracellular
perfusion of the phosphatase inhibitor microcystin revealed that
synaptic GABAA receptors of pyramidal cells, but not those
of GCs, are continually phosphorylated by PKA and conversely,
dephosphorylated, most likely by phosphatase 1 or 2A. This
differential, brain region-specific phosphorylation of
GABAA receptors may produce a wide dynamic range of
inhibitory synaptic strength in these two regions of the hippocampal formation.
Key words:
GABAA; miniature IPSCs; phosphorylation; receptors; PKA; PKC
Copyright © 1999 Society for Neuroscience 0270-6474/99/192674-10$05.00/0
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