Abstract
A large body of work now shows the importance of GABAA receptor-mediated tonic inhibition in regulating CNS function. However, outside of pathological conditions, there is relatively little evidence that the magnitude of tonic inhibition is itself under regulation. Here we review the mechanisms by which tonic inhibition is known to be modulated, and outline the potential behavioral consequences of this modulation. Specifically, we address the ability of protein kinase A and C to phosphorylate the extrasynaptic receptors responsible for the tonic GABAA current, and how G-protein coupled receptors can regulate tonic inhibition through these effectors. We then speculate about the possible functional consequences of regulating the magnitude of the tonic GABAA current.
Highlights
GABA is the major inhibitory neurotransmitter in the mammalian forebrain
One of the earliest pieces of evidence that GABAA receptors can be modulated by kinases directly was provided by Sigel et al (1991), who demonstrated that phorbol myristate acetate (PMA) stereo-selectively reduced the amplitude of evoked GABA currents recorded in Xenopus oocytes expressing GABAA receptors with a variety of subunit compositions
We suggest a reason that may come into play is the plasticity afforded to the tonic GABAA receptor system
Summary
Reviewed by: Ivan Pavlov, University College London, Institute of Neurology, UK Jaideep Kapur, University of Virginia, USA. A large body of work shows the importance of GABAA receptor-mediated tonic inhibition in regulating CNS function. Outside of pathological conditions, there is relatively little evidence that the magnitude of tonic inhibition is itself under regulation. We review the mechanisms by which tonic inhibition is known to be modulated, and outline the potential behavioral consequences of this modulation. We address the ability of protein kinase A and C to phosphorylate the extrasynaptic receptors responsible for the tonic GABAA current, and how G-protein coupled receptors can regulate tonic inhibition through these effectors. We speculate about the possible functional consequences of regulating the magnitude of the tonic GABAA current
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