Site-specific splice variation of the human P2X(4) receptor

P2X(4) receptors are expressed in specific brain areas. We now describe sit e-specific splice variations of the human P2X(4) receptor subunit occurring at residue [YV\(G) under bar down arrow 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 1 30 amino acids, including six of the 10 conserved extracellular cysteine re sidues. Transfection of P2X(4(a)), but not p2X(4(c)), formed functional cha nnels in Xenopus oocytes and human 1321N1 cells. After transfection of p2X( 4(b)) small, inconsistent ATP-evoked responses were detected only in the hu man cef Is, 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 fun ctions of the human P2X(4) receptor may be altered by alternative splicing, (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.