Negative cross talk between anionic GABA(A) and cationic P2X ionotropic receptors of rat dorsal root ganglion neurons

Using whole-cell patch-clamp recording and intracellular Ca2+ imaging of ra t cultured DRG neurons, we studied the cross talk between GABA(A) and P2X r eceptors. A rapidly fading current was the main response to ATP, whereas GA BA elicited slowly desensitizing inward currents. Coapplication of these ag onists produced a total current much smaller than the linear summation of i ndividual responses (68 +/- 5% with 10 muM ATP plus 100 muM GABA). Occlusio n was observed regardless of ATP response type. Neurons without functional P2X receptors manifested no effect of ATP on GABA currents (and vice versa) . Occlusion was also absent in the presence of the P2X blocker trinitrophen yl-ATP (TNP-ATP) or of the GABA blocker picrotoxin, indicating a lack of in volvement by metabotropic ATP or GABA receptors. Less occlusion was obtaine d when ATP was applied 2 sec after GABA than when GABA was applied after AT P. Changing the polarity of GABA currents by using intracellular SO42- inst ead of Cl- significantly reduced the occlusion of ATP currents by GABA, sug gesting an important role for Cl- efflux in this phenomenon. Occlusion was enhanced whenever intracellular Ca2+ ([Ca2+](i)) was not buffered, indicati ng the cross talk-facilitating role of this divalent cation. Ca2+ imaging s howed that ATP (but not GABA) increased [Ca2+](i) in voltage-clamped or int act neurons. Our data demonstrated a novel Cl- and Ca2+-dependent interacti on between cationic P2X and anionic GABA(A) receptors of DRG neurons. Such negative cross talk might represent a model for a new mechanism to inhibit afferent excitation to the spinal cord as GABA and ATP are coreleased withi n the dorsal horn.