Activation of P2X4 receptors induces an increase in the area of the extracellular region and a decrease in receptor mobility

FEBS Letters

article

Frederik Bergler¹  Christian Fuentes¹  Fahim Kadir¹  Camilo Navarrete¹  Jack Supple¹  Nelson P. Barrera²  John Michael Edwardson¹ 

[1] Department of Pharmacology, University of Cambridge;Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile

关键词: atomic force microscopy;    fast-scan imaging;    P2X receptor;    receptor activation;    receptor mobility;   

DOI  :  10.1002/1873-3468.13942

来源: John Wiley & Sons Ltd.

【 摘 要 】

The P2X4 receptor (P2X4R) is an ATP-gated cation channel. Here, we used fast-scan atomic force microscopy (AFM) to visualize changes in the structure and mobility of individual P2X4Rs in response to activation. P2X4Rs were purified from detergent extracts of transfected cells and integrated into lipid bilayers. Activation resulted in a rapid (2 s) and substantial (10–20 nm2 ) increase in the cross-sectional area of the extracellular region of the receptor and a corresponding decrease in receptor mobility. Both effects were blocked by the P2X4R antagonist 5-BDBD. Addition of cholesterol to the bilayer reduced receptor mobility, although the ATP-induced reduction in mobility was still observed. We suggest that the observed responses to activation may have functional consequences for purinergic signalling.

【 授权许可】

Unknown