Inhibitory interaction between P2X4 and GABAC ρ1 receptors

Reciprocal functional inhibition between P2X and GABAA/C receptors represents a novel mechanism fine-tuning neuronal excitability. However, the participating receptors and underlying mechanisms are not fully understood. P2X4 receptor is widely found in neurons that express GABAC ρ1 receptor. Thus, we co-expressed P2X4 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 (IATP+GABA) were significantly smaller compared to the addition of IATP and IGABA. Furthermore, IATP were strongly suppressed during ρ1 receptor activation. Similarly, IGABA were greatly attenuated during P2X4 receptor activation. Such mutual inhibition was absent in cells only expressing P2X4 or ρ1 receptor. Taken together, these functional data support negative cross-talk between P2X4 and ρ1 receptors.