A Mechanism-Based Approach to P2X7 Receptor Action
1Department of Biophysics (M.U.) and Department of Pharmacology (O.U.), Faculty of Medicine, Ankara University, Ankara, Turkey mugur@medicine.ankara.edu.tr.
Molecular Pharmacology
|February 10, 2019
Summary
The P2X7 receptor, a ligand-gated ion channel, exhibits unusual cell responses beyond ion flux. This review explores less understood P2X7 receptor mechanisms, including large molecule permeation and signaling pathway activation.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- The P2X7 receptor is a widespread ligand-gated ion channel known for unique cellular responses.
- While Ca2+ influx and K+ efflux are understood, other P2X7 receptor mechanisms remain unclear.
- The P2X7 receptor's role in cell membrane permeabilization to large molecules is a key area of investigation.
Purpose of the Study:
- To review and assess emerging data on the P2X7 receptor's less understood activation mechanisms.
- To highlight the potential significance of these mechanisms in cellular physiology and disease.
- To draw attention to alternative hypotheses beyond the 'pore formation' model.
Main Methods:
- Literature review and critical assessment of existing data.
- Analysis of functional data on P2X7 receptor-mediated permeation and signaling.
- Comparison of different models for P2X7 receptor activation.
Main Results:
- Evidence suggests large molecules may pass directly through the P2X7 receptor pore, particularly cationic molecules.
- Some cell types show P2X7 receptor-mediated permeation of anionic large molecules via a separate pathway.
- The P2X7 receptor may directly activate other signaling molecules or ion channels, independent of pore formation.
Conclusions:
- The P2X7 receptor's function extends beyond simple ion flux, involving complex permeation and signaling pathways.
- Understanding these alternative mechanisms is crucial for comprehending P2X7 receptor roles in physiology, such as neurotransmitter release.
- Further research into these neglected P2X7 receptor actions could reveal novel therapeutic targets.
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