γ-Aminobutyric acid (GABA) from satellite glial cells tonically depresses the excitability of primary afferent fibers

Primary afferent fibers express extrasynaptic GABA(A) and GABA(B) receptors in the axons and soma. However, whether these receptors are tonically activated by ambient GABA and the source of the neuro-transmitter is presently unknown. Here, we show that GABA release from dorsal root ganglia (DRG) does not depend on extracellular calcium, but depends upon calcium released from intracellular stores, and is mediated by Best1 channels. Using a preparation consisting of the spinal nerve in continuity with the DRG and the dorsal root, we found that endogenous GABA tonically activates GABA receptors, depressing the excitability of the primary afferents. In addition, using HPLC we found that GABA is released in the DRG, and by immunofluorescence microscopy we show the presence of GABA, the Best1 channel, and some enzymes of the putrescine pathway of GABA biosynthesis, in glutamine synthase- and GFAP-positive satellite glial cells. Last, we found that the blockade of the Best1 channel activity reduced the excitability of primary afferents and prevented the activation of the GABA receptors. These results suggest that satellite glial cells may be the source of endogenous GABA released in the DRG via Best1 channels, which tonically activates extrasynaptic GABA receptors. (C) 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

Automated summary

Primary afferent fibers express extrasynaptic GABA(A) and GABA(B) receptors, with GABA released through Best1 channels in the DRG tonically activating these receptors and decreasing fiber excitability. Satellite glial cells are suggested as the possible source of endogenous GABA released via Best1 channels in the DRG.