Is pannexin the pore associated with the P2X7 receptor?

Is pannexin the pore associated with the P2X7 receptor?

The P2X7 receptor (P2X7R), an ATP-gated cation channel, is expressed predominantly in leukocytes. Activation of P2X7R has been implicated in the formation of a cytolytic pore (i.e., a large conductance channel) that allows the passage of molecules up to 900 Da in macrophages. At least two hypotheses...

Full description

Saved in:
Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology Vol. 386; no. 9; pp. 775 - 787
Main Authors: Alberto, A. V. P., Faria, R. X., Couto, C. G. C., Ferreira, L. G. B., Souza, C. A. M., Teixeira, P. C. N., Fróes, M. M., Alves, L. A.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2013
Springer Nature B.V
Subjects:
Adenosine Triphosphate - pharmacology
Animals
Biomedical and Life Sciences
Biomedicine
Cell Line
Cells, Cultured
Connexins - physiology
Macrophages, Peritoneal - physiology
Male
Mice
Nerve Tissue Proteins - physiology
Neurosciences
Original Article
Pharmacology/Toxicology
Purinergic P2X Receptor Antagonists - pharmacology
Rats
Rats, Wistar
Receptors, Purinergic P2X7 - physiology
Connexin
Hemichannels
Pannexin
Pore
Gap junctions
Gap junction antagonists
Electrophysiology
P2X7 receptor
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The P2X7 receptor (P2X7R), an ATP-gated cation channel, is expressed predominantly in leukocytes. Activation of P2X7R has been implicated in the formation of a cytolytic pore (i.e., a large conductance channel) that allows the passage of molecules up to 900 Da in macrophages. At least two hypotheses have been presented to explain the conversion of a nonselective cation channel to a cytolytic pore. One hypothesis suggests that the pore is a separate molecular structure activated by P2X7R, and the second asserts that this is an intrinsic property of P2X7R (pore dilation). Based on connexin knockout and hemichannel antagonist studies, some groups have concluded that connexins and pannexins, the hemichannel-forming proteins in vertebrates, are fundamental components of the large conductance channel associated with P2X7R. Dye uptake and electrophysiology experiments were used to evaluate the efficacy and specificity of some hemichannel antagonists under conditions known to open the large conductance channel associated with P2X7R. Hemichannel antagonists and interference RNA (RNAi) targeting pannexin-1 did not affect P2X7R macroscopic currents [ATP, 1,570 ± 189 pA; ATP + 100 μM carbenoxolone (CBX), 1,498 ± 100 pA; ATP + 1 mM probenecid (Prob), 1,522 ± 9 pA] or dye uptake in a FACS assay (ATP, 63 ± 5 %; ATP + 100 μM CBX, 51.51 ± 8.4 %; ATP + 1 mM Prob, 57.7 ± 4.3 %) in mouse macrophages. These findings strongly suggest that the high-permeability pore evident after prolonged P2X7R activation does not occur through connexin or pannexin hemichannels in murine macrophages. Another membrane protein may be involved in P2X7R pore formation.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-013-0868-x