NG2 glial cells are equipped with functional AMPA and GABA_A receptors and receive direct synaptic input from glutamatergic and GABAergic neurons. The functional impact of these neuron-glia synapses is still unclear. Therefore we combined functional and molecular techniques to analyse properties of GABA_A receptors in NG2 cells.

GABA activated slowly desensitizing receptor responses in NG2 cells. The GABA_A receptor agonist, muscimol, mimicked GABA-induced responses. Receptor currents were blocked by the GABA_A receptor antagonist, bicuculline. To elucidate the GABA_A receptor subunit composition, we tested their modulation by benzodiazepines and barbiturates. Pentobarbital increased GABA-evoked responses about threefold. Preincubation of benzodiazepines, modulators of GABA_A receptors, increased the receptor responses about twofold, while zolpidem, a modulator of a1 to a3 subunits, potentiated the GABA receptor responses at nM concentration. Micromolar concentrations of Zn²⁺ blocked GABA responses effectively. Modulation of the responses by benzodiazepines and blocking by Zn²⁺ strongly suggested expression of the g2 receptor subunit. To further identify the receptor subunits, single cell transcript analysis was performed subsequent to functional characterization. The subunits a1, a 2, b3, and g1, g2 were most abundantly expressed.

To determine the effect of GABA_A receptor activation on membrane potential, perforated patches were obtained from NG2 cells in situ. In the current-clamp mode, maximal activation of the GABA-mediated Cl^- conductance depolarized the NG2 cells to 20 ± 6 mV (n = 6) corresponding to [Cl^-]_i of about 60 mM. The GABA-induced depolarization might trigger Ca²⁺ influx through voltage-activated Ca²⁺ channels in the NG2 glial cells.

Supported by DFG (SFB/TR3, SE 774/3).