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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Bergler, Frederik 
Fuentes, Christian 
Kadir, Md Fahim 
Navarrete, Camilo 
Supple, Jack 

Abstract

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.

Description

Keywords

P2X receptor, atomic force microscopy, fast-scan imaging, receptor activation, receptor mobility, Adenosine Triphosphate, Animals, Cholesterol, HEK293 Cells, Humans, Lipid Bilayers, Microscopy, Atomic Force, Movement, Rats, Receptors, Purinergic P2X4, Signal Transduction

Journal Title

FEBS Lett

Conference Name

Journal ISSN

0014-5793
1873-3468

Volume Title

594

Publisher

Wiley