A ROLE FOR CALCINEURIN IN THE DESENSITIZATION OF THE P2X(3) RECEPTOR

THE sensory neurone-specific ATP-gated cation channel P2X(3), when exp ressed in Xenopus oocytes, desensitizes rapidly. Complete removal of e xtracellular calcium abolishes desensitization. Pretreatment of oocyte s with cyclosporin also abolishes P2X(3) desensitization. When the cal cineurin auto-inhibitory peptide (CaN A457-481) was injected into oocy tes, the rate of desensitization of P2X(3) decreased on consecutive ap plications of ATP, suggesting a role for calcineurin in the regulation of desensitization. Truncated P2X(3) clones initiating at Met-75 lack the N-terminal intracellular region, but express functional channels in oocytes that do not desensitize. Taken together, these data suggest that P2X(3) desensitizes through a calcium-dependent calcineurin-medi ated dephosphorylation involving N-terminal residues that are phosphor ylated in functional channels.