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Neuroscience. 2017 Jun 3;352:1-8. doi: 10.1016/j.neuroscience.2017.03.037. Epub 2017 Apr 1.

Disrupting sensitization of TRPV4.

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Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Germany.
Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Germany; Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. Electronic address:


TRPV4 ion channels have a broad expression profile and were shown to contribute to enhanced pain sensation in inflammation. Directly blocking TRPV4 might run the risk of interfering with normal physiology, and has prompted to explore the interaction with the scaffolding protein AKAP79, an approach successfully used for TRPV1 channels. HEK293t cells express AKAP79, additional transfection did not sensitize human TRPV4. Application of trypsin facilitated responses to TRPV4 agonist GSK1016790A. Using a specific protease-activated receptor 2 agonist, involvement of an A-kinase anchoring protein in TRPV4 activation was demonstrated by inhibition with AKAP inhibitor peptide Ht31. TRPV4 has substantial sequence similarity to TRPV1 in the range interacting with AKAP79. A synthetic peptide, resembling these amino acids and extended by a positive region for transmembrane uptake, was tested. Sensitization of TRPV4 responses could be reduced after exposure to this 771-781::TAT peptide but not by a scrambled control peptide. This validates the concept of targeting the interaction between TRPV4 and AKAP79 and controlling increased TRPV4 activity.


AKAP; TRP channel; inflammation; protein–protein interaction; sensitization

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