The Functional Role of Spontaneously Opening GABA Receptors in Neural Transmission.

Ionotropic type of γ-aminobutyric acid receptors (GABARs) produce two forms of inhibitory signaling: phasic inhibition generated by rapid efflux of neurotransmitter GABA into the synaptic cleft with subsequent binding to GABARs, and tonic inhibition generated by persistent activation of extrasynaptic and/or perisynaptic GABARs by GABA continuously present in the extracellular space. It is widely accepted that phasic and tonic GABAergic inhibition is mediated by receptor groups of distinct subunit composition and modulated by different cytoplasmic mechanisms. Recently, however, it has been demonstrated that spontaneously opening GABARs (s-GABARs), which do not need GABA binding to enter an active state, make a significant input into tonic inhibitory signaling. Due to GABA-independent action mode, s-GABARs promise new safer options for therapy of neural disorders (such as epilepsy) devoid of side effects connected to abnormal fluctuations of GABA concentration in the brain. However, despite the potentially important role of s-GABARs in neural signaling, they still remain out of focus of neuroscience studies, to a large extent due to technical difficulties in their experimental research. Here, we summarize present data on s-GABARs functional properties and experimental approaches that allow isolation of s-GABARs effects from those of conventional (GABA-dependent) GABARs.