ATP functions as a neurotransmitter and a neuromodulator in various tissues by acting on metabotropic (P2Y) and ionotropic (P2X) receptors. Evidence suggests that ATP activates P2X receptors on several cell types in the organ of Corti of guinea pig including outer hair cells (OHCs), Deiters' cells, Hensen's cells, pillar cells and inner hair cells (IHCs). Determining the sequence and structure of P2X receptors in guinea pig organ of Corti is important for understanding the function of ATP in the cochlea. We screened a guinea pig organ of Corti cDNA library for P2X2 ATP receptors using rat P2X2 cDNA as a probe. We sequenced three P2X2 variants which were found to be abundant in this library. One is a novel P2X2 isoform (P2X2-3) created by a retained intron coding for an additional 27 amino acids (81 bp) in the putative extracellular domain. We have also sequenced a variant (P2X2-2) that lacks both the 81-bp sequence and a 192-bp sequence in the 3' intracellular domain. A third variant (P2X2-1) contains the intracellular 192-bp sequence but not the extracellular 81-bp sequence found in P2X2-3. The multiple transcripts arise from alternative intron and exon splicing events. In situ hybridization with a probe common to the three variants localized P2X2 to many of the cells of the organ of Corti.