Guinea‐pig sympathetic neurons express varying proportions of two distinct P2X receptors

1 Characterization of P2X receptors on neurons of guinea‐pig superior cervical ganglion (SCG) has been carried out using a whole‐cell voltage‐clamp technique. 2 Application of ATP and α,β‐methylene ATP (αβ‐MeATP) produced fast activating inward currents, which desensitized slowly. The maximum response to αβ‐MeATP was 36 ± 23 % (range 0·1‐100 %) of that evoked by ATP in the same cell. 3 Co‐application of αβ‐MeATP (300 μM) with ATP (300 μM) produced a response that was 97 ± 1 % of that given by ATP alone. Following desensitization with αβ‐MeATP, the decrease in response to ATP was equal to the absolute reduction in response to αβ‐MeATP in the same cell. 4 The concentration‐response curve for αβ‐MeATP had an EC 50 of 42 μM and a Hill coefficient of 1·17. For cells where the ratio of αβ‐MeATP/ATP currents at 100 μM was < 0·1, the ATP concentration‐response curve had an EC 50 of 56 μM and a Hill coefficient of 1·95. However, in cells where the ratio was > 0·7, the curve had an EC 50 of 60 μM and a Hill coefficient of 0·97. 5 The response to 100 μM αβ‐MeATP was inhibited by 2′ (or 3′)‐ O‐ trinitrophenyl‐ATP (TNP‐ATP) with an IC 50 of 70 nM. However, on cells where the ratio of αβ‐MeATP/ATP currents was < 0·1, ATP was inhibited by TNP‐ATP with an IC 50 of 522 nM. 6 Immunohistochemical staining with antibodies raised against rat P2X 2 and P2X 3 epitopes suggested that both subunits were expressed by guinea‐pig SCG neurons. 7 We conclude that varying proportions of two distinct P2X receptors coexist on the cell bodies of individual guinea‐pig SCG neurons, which may correspond to homomeric P2X 2 and heteromeric P2X 2/3 receptors.