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Updated: May 11, 2026
16:36
Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 18, 2009
Is pannexin the pore associated with the P2X7 receptor?
A V P Alberto1, R X Faria, C G C Couto
1Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365 Manguinhos, CEP: 21045-900, Rio de Janeiro, RJ, Brazil.
Naunyn-Schmiedeberg'S Archives of Pharmacology
|May 10, 2013
Summary
The P2X7 receptor (P2X7R) forms a large pore in macrophages, but this pore does not involve connexins or pannexins. Further research is needed to identify the specific membrane proteins responsible for P2X7R pore formation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The P2X7 receptor (P2X7R) is an ATP-gated ion channel primarily found in leukocytes.
- P2X7R activation in macrophages can lead to the formation of a large conductance channel, allowing passage of molecules up to 900 Da.
- Two hypotheses exist for this pore formation: a separate structure activated by P2X7R or an intrinsic pore dilation property of P2X7R.
Purpose of the Study:
- To investigate the role of connexins and pannexins in P2X7R-mediated large conductance channel formation.
- To evaluate the efficacy and specificity of hemichannel antagonists and pannexin-1 interference RNA (RNAi) in murine macrophages.
Main Methods:
- Utilized dye uptake assays (FACS) and electrophysiology to measure P2X7R macroscopic currents and pore formation.
- Employed hemichannel antagonists (carbenoxolone, probenecid) and pannexin-1 RNAi under conditions of P2X7R activation.
Main Results:
- Hemichannel antagonists and pannexin-1 RNAi did not significantly alter P2X7R macroscopic currents or dye uptake.
- Observed P2X7R currents were 1,570±189 pA (ATP), 1,498±100 pA (ATP+CBX), and 1,522±9 pA (ATP+Prob).
- Dye uptake was 63±5% (ATP), 51.51±8.4% (ATP+CBX), and 57.7±4.3% (ATP+Prob).
Conclusions:
- Connexin and pannexin hemichannels are not essential components of the P2X7R-associated high-permeability pore in mouse macrophages.
- The formation of the P2X7R-induced pore likely involves other, yet unidentified, membrane proteins.
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