Glycine and GABA(A) receptor-mediated chloride fluxes in synaptoneurosomes from different parts of the rat brain

Strychnine-sensitive, inhibitory glycine receptors have not until lately been considered to play a significant role in neurotransmission in mammalian forebrain regions. In order to investigate the role of glycine as a neurotransmitter in brain we have measured glycine induced chloride fluxes in different adult rat forebrain areas using synaptoneurosomes and a chloride-sensitive fluorescent indicator. The results have been compared to those obtained with GABA. The synaptoneurosomes from every brain area investigated responded to both glycine and GABA with chloride fluxes in a picrotoxin sensitive manner. The effect of glycine was inhibited by strychnine, which had no effect on the GABA-induced Cl- flux. Bicuculline inhibited the effect of GABA, but had no effect on the glycine-induced Cl- flux. Addition of GABA did not affect the response to glycine and vice versa. The endogenous content of glycine and GABA in the synaptoneurosome preparations was about the same and synaptoneurosomes from every brain area investigated released both glycine and GABA upon depolarisation with KCl. The depolarisation induced release of both GABA and glycine was partly Ca2+-dependent and partly Ca2+-independent. These results indicate that glycine can induce inhibitory Cl- fluxes distinct from GABA induced fluxes in every investigated brain area and that glycine can be released upon depolarisation.