Journal of Biological Chemistry
Volume 283, Issue 8, 22 February 2008, Pages 5110-5117
Journal home page for Journal of Biological Chemistry

Membrane Transport, Structure, Function, and Biogenesis
On the Role of the First Transmembrane Domain in Cation Permeability and Flux of the ATP-gated P2X2 Receptor*

https://doi.org/10.1074/jbc.M708713200Get rights and content
Under a Creative Commons license
open access

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.

Cited by (0)

*

This work was supported by grants from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1

Present address: Dept. of Brain Neurophysiology, Hirosaki University Graduate School of Medicine, 5 Zaifutyo, Hirosaki City, Aomori 036-8562, Japan.