P2X7 receptors are nonselective cation channels opened by extracellular ATP. They are mainly expressed in cells of the immune system and in some epithelia. P2X7 receptors are supposed to assemble as trimers of homomeric P2X7 subunits. A splice variant of the human P2X7 receptor subunit (hP2X7B) was recently identified which lacks the intracellular C-terminal tail of the wt receptor subunit (hP2X7A). In the Xenopus laevis oocyte expression system we investigated the electrophysiological characteristics of hP2X7A and B receptors. hP2X7A and B receptor isoforms mediated typical exponentially saturating and non-desensitizing currents during ATP application. Coexpression of hP2X7A and B, however, resulted in a strongly desensitizing phenotype indicating an interaction between both splice variants. To provide biochemical evidence for the co- assembly human P2X7A and B isoforms, we co- expressed in Xenopus laevis oocytes double-tagged P2X7A-His-StrepII (bearing a nine residue StrepII sequence C-terminal to the C-terminal hexahistidine tag) together with the His-P2X7B as bait and prey, respectively. Proteins were affinity-purified under non-denaturing conditions, resolved by SDS-PAGE, and visualized by autoradiography. Purification by Strep-Tactin chromatography led to the co-isolation of the non- StrepII-tagged His-P2X7B with P2X7A- His-StrepII, and reciprocally P2X7A-His with P2X7B-StrepII. We conclude from these data that P2X7A and P2X7B are capable of coassembling to form P2X7A/P2X7B heterotrimers.