Inhibitory interaction between P2X4 and GABA(C) rho1 receptors.

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) rho1 receptor. Thus, we co-expressed P2X(4) and rho1 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 rho1 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 rho1 receptor. Taken together, these functional data support negative cross-talk between P2X(4) and rho1 receptors.