Feature Article: Selective modulation of tonically active GABA A receptor functional subgroups by G-proteins and protein kinase C

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 243; no. 13; p. 1046
• Main Authors: O'Neill, Nathanael, Sylantyev, Sergiy
• Format: Journal Article
• Language: English
• Published: England 01.09.2018
• Subjects: tonic inhibitory current; action potential generation; Spontaneously opening GABAA receptors; G-proteins; protein kinase C
• ISSN: 1535-3699

Here we study intracellular mechanisms which regulate inhibitory signaling delivered through continuously (tonically) open ionotropic receptors of γ-aminobutyric acid (GABA) of dentate gyrus granule cells (DGCs). We found that, apart of classical GABA-A receptors (GABA Rs) which can be activated by GABA binding, a significant part of tonic inhibitory current is delivered by newly discovered spontaneously opening GABA Rs (s-GABA Rs), which enter active state without binding of GABA. We have also found that conventional GABA Rs and s-GABA Rs are regulated by different intracellular mechanisms, which may overlap and thus induce various signaling repercussions. Our results demonstrate that s-GABA Rs play a key role in the mechanism that implements DGCs functional role in the brain. On top of that, since regulatory mechanisms under study are affected in a number of pathological states, our results may have broad implications for treatment of neurological disorders.