The P2X7 receptor is an ATP-sensitive ligand-gated cation channel, expressed predominantly in cells with immune origin. Recent studies have demonstrated that P2X7 may play an important role in pain signaling. In the present study, the expression of P2X7 receptors in non-neuronal cells and neurons isolated from dorsal root ganglia was characterized using patch clamp, pharmacological and confocal microscopy approaches. In small diameter DRG neurons, 100 microM 2', 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) evoked an inward current, which was inhibited completely by 1 microM A-317491, a potent and selective P2X3 receptor antagonist. In contrast, BzATP evoked concentration-dependent increases in inward currents in non-neuronal DRG cells with an EC50 value of 26 +/- 0.14 microM, which were resistant to the blockade by A-317491. The activity to evoke cationic currents by P2X receptor agonists in non-neuronal cells showed a rank order of BzATP > ATP > alpha,beta-meATP. Pyridoxal-phosphate-6-azophenyl-,2',4'-disulphonic acid (PPADS) and Mg2+ produced concentration-dependent inhibition of BzATP-evoked currents in non-neuronal cells. Confocal microscopy revealed positive immunoreactivity of anti-P2X7 receptor antibodies on non-neuronal cells. No anti-P2X7 immunoreactivity was observed on DRG neurons. Further electrophysiological studies showed that prolonged agonist activation of P2X7 receptors in non-neuronal cells did not lead to cytolytic pore formation. Taken together, the present study demonstrated functional expression of P2X7 receptors in non-neuronal but not in small diameter neurons from rat DRG. Modulation of P2X7 receptors in non-neuronal cells might have impact on peripheral sensory transduction under normal and pathological states.