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Emerging Concepts in Ion Channel Biophysics
Thursday Speaker Abstracts
28
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.