Intracellular disulfide bond that affects ATP responsiveness of P2X2 receptor/channel.

The role of intracellular cysteine residues in P2X(2) receptor/channel was investigated. When dithiothreitol was intracellularly applied, both the maximal response and the sensitivity of the wild-type channel to ATP were decreased. On the other hand, Cu(2+) phenanthroline did not affect the responsiveness. When two intracellular cysteine residues (Cys(9) and Cys(430)) were replaced with alanine, both the maximal response and the sensitivity was decreased with the replacement at Cys(9), whereas no such decrease was observed with the replacement at Cys(430). These results suggest that an intracellular disulfide bond involving Cys(9) regulates the responsiveness of P2X(2) receptor/channel to ATP.