Differential regulation of synaptic and extrasynaptic α4 GABA(A) receptor populations by protein kinase A and protein kinase C in cultured cortical neurons

Neuropharmacology
J Peyton BohnsackA Leslie Morrow

Abstract

The GABAA α4 subunit exists in two distinct populations of GABAA receptors. Synaptic GABAA α4 receptors are localized at the synapse and mediate phasic inhibitory neurotransmission, while extrasynaptic GABAA receptors are located outside of the synapse and mediate tonic inhibitory transmission. These receptors have distinct pharmacological and biophysical properties that contribute to interest in how these different subtypes are regulated under physiological and pathological states. We utilized subcellular fractionation procedures to separate these populations of receptors in order to investigate their regulation by protein kinases in cortical cultured neurons. Protein kinase A (PKA) activation decreases synaptic α4 expression while protein kinase C (PKC) activation increases α4 subunit expression, and these effects are associated with increased β3 S408/409 or γ2 S327 phosphorylation respectively. In contrast, PKA activation increases extrasynaptic α4 and δ subunit expression, while PKC activation has no effect. Our findings suggest synaptic and extrasynaptic GABAA α4 subunit expression can be modulated by PKA to inform the development of more specific therapeutics for neurological diseases that involve deficits in GABAergic tr...Continue Reading

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Citations

Feb 10, 2016·The Journal of Pharmacology and Experimental Therapeutics·Stephen L CarlsonA Leslie Morrow
Feb 16, 2018·Frontiers in Cellular Neuroscience·Elena García-MartínJosé A G Agúndez
Jul 19, 2018·The Journal of Physiology·Andre H LagrangeRobert L Macdonald
Mar 10, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·John Peyton BohnsackA Leslie Morrow
Mar 13, 2019·Alcoholism, Clinical and Experimental Research·Benjamin A HughesA Leslie Morrow
Aug 12, 2017·The Journal of Pharmacology and Experimental Therapeutics·John Peyton BohnsackA Leslie Morrow
May 15, 2018·Frontiers in Molecular Neuroscience·Juan ChenYi Shen
Oct 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Milena JankowskaMaria Stankiewicz
Jan 3, 2018·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hua-Jun Feng, Stuart A Forman

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