We report here the cloning of a chicken cDNA (402 aa) showing high sequence similarity to the previously cloned rat and human P2X(5) receptors (67 and 69%, respectively). The chicken P2X(5) subunit is encoded by a gene composed of 12 translated exons, which shows conserved genomic structure with mammalian P2X genes. In HEK-293 cells heterologously expressing chicken P2X(5) receptors, ATP activates a current that desensitizes in a way that is dependent on the presence of extracellular divalent cations. ATP and 2-methylthio ATP are equipotent agonists (EC(50) approximately 2 microM) and suramin and pyridoxal 5-phosphate-6-azophenyl-2',4'-disulfonic acid are potent antagonists. Additionally, reversal potential measurements indicate that chicken P2X(5) is permeable not only to cations but also to chloride (P(Cs+)/P(Cl-) approximately 1.9), as has been described for native P2X receptor mediated responses in embryonic chicken skeletal muscle. mRNA distribution of chicken P2X(5) was determined by in situ hybridization analysis in both whole embryos and on tissue slices of heart and skeletal muscle. Our results suggest that chicken P2X(5) receptors are expressed in developing muscle and might play a role in early muscle differentiation.