Functional characterization of mutants in the transmembrane domains of the rat P2X7 receptor that regulate pore conductivity and agonist sensitivity

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F15%3A10293163" target="_blank" >RIV/00216208:11310/15:10293163 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/15:00446301

Result on the web

<a href="http://onlinelibrary.wiley.com/doi/10.1111/jnc.13078/pdf" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1111/jnc.13078/pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jnc.13078" target="_blank" >10.1111/jnc.13078</a>

Result language

angličtina

Original language name

Functional characterization of mutants in the transmembrane domains of the rat P2X7 receptor that regulate pore conductivity and agonist sensitivity

Original language description

In the sustained presence of agonist, the opening of P2X7R channel is followed by pore dilatation, which causes an increase in its permeability to larger organic cations, accompanied by receptor sensitization. To explore the molecular mechanisms by which the conductivity and sensitivity are increased, we analyzed the electrophysiological properties and YO-PRO-1 uptake of selected alanine mutants in the first and second transmembrane domains of the rat P2X7R. Substitution of residues Y40, F43, G338 and D352 with alanine reduced membrane trafficking, and the D352A was practically nonfunctional. The Y40A and F43A mutants that were expressed in the membrane lacked pore dilation ability. Moreover, the Y40A and Y40F displayed desensitization, whereas the Y40W partially recovered receptor function. The G338A/S mutations favored the open state of the channel and displayed instantaneous permeability to larger organic cations. The G338P was nonfunctional. The L341A and G345A displayed normal trafficking, current amplitude and sensitization, but both mutations resulted in a decreased pore formation and dye uptake. These results showed that the increase in P2X7R conductivity and sensitivity is critically dependent on residues Y40 and F43 in the TM1 domain and that the region located at the intersection of TM2 helices controls the rate of large pore opening.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

ED - Physiology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Neurochemistry

ISSN

0022-3042

e-ISSN

—

Volume of the periodical

133

Issue of the periodical within the volume

6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

815-827

UT code for WoS article

000356011300005

EID of the result in the Scopus database

2-s2.0-84925321521