P2X receptors (P2XRs) are trimeric ATP-gated cation channels. Seven Subunits have been cloned. P2X4 and P2X7 Subunits show overlapping expression and both Subunits are involved in pathophysiological processes such as inflammatory and neuropathic pain. A recent study provides evidence for heteromeric P2X4/7Rs. In this study, subtype-specific antibodies in combination with BN-PAGE are used to directly visualize P2XR complexes solubilized from membrane extracts of native tissues. The results show specific P2X7R and P2X4R staining in many tissues. The P2X7 complex has a clearly different size than the P2X4 complex but is likewise composed of three subunits. No complexes corresponding to more than three subunits could be detected. Also, no complexes of intermediate size or reactive to both antibodies were detected. These data suggest that either heteromerization between P2X4 and P2X7 subunits results not in stable heteromeric complexes or P2X4/7 heteromers do not represent a dominant subtype in the tissues investigated. (C) 2008 Elsevier Inc. All rights reserved.