Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Thursday Speaker Abstracts

Dynamic Regulation of TRPV1 Ion Channels Sharona E. Gordon , Anastasiia Stratiievska. University of Washington, Seattle, WA, USA.

Increased sensitivity to noxious thermal and chemical stimuli in the setting of inflammation is mediated, at least in part, by increased plasma membrane expression of the pain-transducing ion channel TRPV1. We have studied this sensitization using the prototypical inflammatory signal nerve growth factor (NGF), which acts through the receptor tyrosine kinase receptor TrkA. Although TrkA also couples to the MAPK and PLC signaling pathways, we and others have shown that its signaling through PI3K underlies the acute phase of NGF-induced sensitization of TRPV1. Furthermore, we have shown that the ARD of TRPV1 interacts directly with PI3K, but the function of the interaction and its role in sensitization were unknown. We now demonstrate that coexpression with TRPV1 potentiates the activity of PI3K in response to NGF. A fragment corresponding to the N-terminal region of TRPV1, including the ARD, was sufficient to produce the potentiation, suggesting that potentiation may involve an increase in the catalytic activity of PI3K. We are currently examining whether potentiation of PI3K is specific to the ARD of TRPV1.

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