Site-specific splice variation of the human P2X4 receptor

Abstract P2X 4 receptors are expressed in specific brain areas. We now describe site-specific splice variations of the human P2X 4 receptor subunit, occurring at residue [YVI G ↓WVFV(W)] near the end of the first predicted transmembrane domain. p2x 4(b) is formed by the insertion of an additional 16 amino acids. p2x 4(c) is formed by deleting a cassette of 130 amino acids, including six of the 10 conserved extracellular cysteine residues. Transfection of P2X 4(a) , but not p2x 4(c) , formed functional channels in Xenopus oocytes and human 1321N1 cells. After transfection of p2x 4(b) small, inconsistent ATP-evoked responses were detected only in the human cells, but when co-expressed, p2x 4(b) may alter the function of P2X 4(a) in oocytes. The distribution of splice variant RNA within human brain suggests regionally-dependent expression. These data indicate that the functions of the human P2X 4 receptor may be altered by alternative splicing.