Selective modulation of tonically active GABAA receptor functional subgroups by G-proteins and protein kinase C. Issue 13 (September 2018)

• Record Type: Journal Article
• Authors: O'Neill, Nathanael; Sylantyev, Sergiy
• Is Part Of: Experimental biology and medicine. Volume 243:Issue 13(2018)
• Page Start: 1046
• Page End: 1055
• Publication Date: 2018-09
• Subjects: Spontaneously opening GABAA receptors -- tonic inhibitory current -- action potential generation -- G-proteins -- protein kinase C; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370218800980
• Languages: English
• ISSNs: 1535-3702

Abstract

Ionotropic receptors of γ-aminobutyric acid (GABAA Rs) produce two forms of inhibitory signaling: phasic inhibition triggered by activation of synaptic GABAA Rs at GABAergic synapses, and tonic inhibition generated in large part through persistent activation of extrasynaptic GABAA Rs. It has recently been demonstrated that tonic inhibition may also involve spontaneously opening GABAA Rs (s-GABAA Rs) whose activation does not require binding of γ-aminobutyric acid (GABA). Here, we examine intracellular mechanisms modulating GABAA Rs' tonic effects in rat dentate gyrus granule cells (DGCs). Cellular control of s-GABAA Rs-delivered tonic current appears to involve signaling inputs from G-protein-dependent and -independent molecular cascades, whereas tonic GABA-dependent current in DGCs is regulated by protein kinase C. The intracellular agents that modulate s-GABAA R-generated inhibition could thus represent a generic mechanism controlling signal integration in central neural circuits.