One-way cross-desensitization between P2X purinoceptors and vanilloid receptors in adult rat dorsal roof ganglion neurones

1. Capsaicin and ATP can activate ligand-gated cation channels in nocicepti ve rat dorsal root ganglion (DRG) neurones. We have studied cross-desensiti zation between these two agents in rat isolated DRG neurones using the whol e-cell voltage-clamp technique. 2. ATP (10 mu M) activated an inward current in DRG neurones at a holding p otential of -60 mV. ATP evoked 'fast' responses that underwent rapid activa tion and desensitization, 'slow' responses that activated and desensitized more slowly, or responses that displayed a mixture of these two characteris tics. The time course of the response to ATP was not related obviously to c apsaicin sensitivity. 3. Prior application of capsaicin (0.5 mu M) increased the proportion of ce lls displaying only fast responses to ATP (10 mu M) suggesting that cross-d esensitization had occurred between capsaicin and the slow component of the ATP response. Prior desensitization to ATP had no apparent effect on the i nward current response to capsaicin (0.5 mu M). 4. Cross-desensitization between capsaicin and ATP was Ca2+ dependent. 5. Changing the membrane holding: potential (V-h) to +40 mV for a brief per iod before applying ATP at -60 mV had a similar effect to capsaicin, i.e. t he proportion of cells displaying only fast responses to ATP was increased significantly. This effect of depolarization was not Ca2+ dependent. 6. The heterogenity of responses to ATP is probably due to co-expression of homomeric P2X(3) receptors and heteromeric receptors comprising P2X(3) sub units with other P2X subunits. We propose that the change in time course of the ATP response produced by prior desensitization to capsaicin is due to selective cross-desensitization with the heteromeric P2X receptors.