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16:36
Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 19, 2009
Inflammatory mediators potentiate ATP-gated channels through the P2X(3) subunit
M Paukert1, R Osteroth, H S Geisler
1Department of Otolaryngology, Division of Sensory Biophysics, Röntgenweg 11, D-72076 Tübingen, Germany.
The Journal of Biological Chemistry
|March 27, 2001
Summary
Neuropeptides like substance P and bradykinin potentiate P2X3 and P2X2/3 ion channels in pain-sensing neurons. This sensitization, mediated by protein kinases, suggests a mechanism for inflammatory pain.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- P2X3 receptors are ATP-gated ion channels crucial for pain sensation, primarily in dorsal root ganglion nociceptive neurons.
- These channels exhibit rapid desensitization and slow recovery, making their kinetics critical for neuronal excitability.
- Modulation of P2X3 channel kinetics can significantly impact nociceptor susceptibility to ATP.
Purpose of the Study:
- To investigate the modulatory effects of neuropeptides substance P and bradykinin on P2X3 and P2X2/3 receptor channels.
- To elucidate the signaling pathways involved in neuropeptide-mediated potentiation of these ion channels.
Main Methods:
- Electrophysiological recordings of currents mediated by P2X3 and P2X2/3 channels.
- Application of substance P and bradykinin, phorbol ester, and protein kinase inhibitors.
- Site-directed mutagenesis to identify key residues involved in the modulatory mechanism.
Main Results:
- Substance P and bradykinin potentiated currents through P2X3 and P2X2/3 channels.
- The potentiation effect was blocked by protein kinase inhibitors and mimicked by phorbol ester, indicating a role for phosphorylation.
- Mutagenesis data supported the hypothesis of phosphorylation-dependent sensitization.
Conclusions:
- Neuropeptides substance P and bradykinin sensitize nociceptors by potentiating P2X3 and P2X2/3 ion channels.
- Inflammatory mediators likely sensitize nociceptors via phosphorylation of these channels or associated proteins.
- This mechanism provides insight into how inflammation enhances pain perception.
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