Inhibitory interaction between P2X 4 and GABA C ρ1 receptors

Abstract

Reciprocal functional inhibition between P2X and GABA A/C receptors represents a novel mechanism fine-tuning neuronal excitability. However, the participating receptors and underlying mechanisms are not fully understood. P2X 4 receptor is widely found in neurons that express GABA C ρ1 receptor. Thus, we co-expressed P2X 4 and ρ1 receptors in HEK293 cells and, using patch-clamp recording, examined whether they have mutual functional inhibition. Currents evoked by simultaneous application of ATP and GABA ( I ATP+GABA) were significantly smaller compared to the addition of I ATP and I GABA. Furthermore, I ATP were strongly suppressed during ρ1 receptor activation. Similarly, I GABA were greatly attenuated during P2X 4 receptor activation. Such mutual inhibition was absent in cells only expressing P2X 4 or ρ1 receptor. Taken together, these functional data support negative cross-talk between P2X 4 and ρ1 receptors.