P2X receptors are ion channels gated by extracellular ATP. We report here cloning of a P2X 2 receptor splice variant (P2X 2-2) carrying a 207 bp deletion in the intracellular C-terminus and the analysis of the corresponding genomic structure of the P2X 2 gene. P2X 2-2 is as highly expressed as the original P2X 2 sequence in various tissues. ATP-activated currents mediated by heterologous expressed P2X 2 or P2X 2-2 receptors showed significant differences in desensitization time constants and steady-state currents in the continuous presence of ATP. These results imply functional differences between cells differentially expressing these P2X 2 isoforms.