On the Role of the First Transmembrane Domain in Cation Permeability and Flux of the ATP-gated P2X2 Receptor

P2X receptors are a family of seven ligand-gated ion channels (P2X1-P2X7) that open in the presence of ATP. We used alanine-scanning mutagenesis and patch clamp photometry to study the role of the first transmembrane domain of the rat P2X2 receptor in cation permeability and flux. Three alanine-subs...

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Bibliographic Details
Published in:The Journal of biological chemistry 2008-02, Vol.283 (8), p.5110-5117
Main Authors: Samways, Damien S.K., Migita, Keisuke, Li, Zhiyuan, Egan, Terrance M.
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Adenosine Triphosphate - pharmacology
Amino Acid Substitution
Animals
Calcium - metabolism
Cations - metabolism
Cell Line
Humans
Ion Channel Gating - drug effects
Ion Channel Gating - physiology
Ion Transport - drug effects
Ion Transport - physiology
Mutation, Missense
Protein Structure, Tertiary - physiology
Rats
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2X2
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Summary:P2X receptors are a family of seven ligand-gated ion channels (P2X1-P2X7) that open in the presence of ATP. We used alanine-scanning mutagenesis and patch clamp photometry to study the role of the first transmembrane domain of the rat P2X2 receptor in cation permeability and flux. Three alanine-substituted mutants did not respond to ATP, and 19 of the 22 functional receptors resembled the wild-type receptor with regard to the fraction of the total ATP-gated current carried by calcium or the permeability of calcium relative to cesium. The remaining three mutants showed modest changes in calcium dynamics. Two of these occurred at sites (Gly30 and Phe44) that are unlikely to interact with permeating cations in a meaningful way. The third was a conserved tyrosine (Tyr43) that may form an inter-pore binding site for calcium. The data suggest that, with the possible exception of Tyr43, the first transmembrane domain contributes little to the permeation properties of the P2X2 receptor.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M708713200