Article abstract
Nature Neuroscience 11, 555 - 564 (2008)
Published online: 6 April 2008 | doi:10.1038/nn.2102
TRPV1 shows dynamic ionic selectivity during agonist stimulation
Man-Kyo Chung1, Ali D Güler1 & Michael J Caterina1
Abstract
Transient receptor potential vanilloid 1 (TRPV1) is an ion channel that is gated by noxious heat, capsaicin and other diverse stimuli. It is a nonselective cation channel that prefers Ca2+ over Na+. These permeability characteristics, as in most channels, are widely presumed to be static. On the contrary, we found that activation of native or recombinant rat TRPV1 leads to time- and agonist concentration–dependent increases in relative permeability to large cations and changes in Ca2+ permeability. Using the substituted cysteine accessibility method, we saw that these changes were attributable to alterations in the TRPV1 selectivity filter. TRPV1 agonists showed different capabilities for evoking ionic selectivity changes. Furthermore, protein kinase C–dependent phosphorylation of Ser800 in the TRPV1 C terminus potentiated agonist-evoked ionic selectivity changes. Thus, the qualitative signaling properties of TRPV1 are dynamically modulated during channel activation, a process that probably shapes TRPV1 participation in pain, cytotoxicity and neurotransmitter release.
- Departments of Biological Chemistry and Neuroscience, Center for Sensory Biology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
Correspondence to: Michael J Caterina1 e-mail: caterina@jhmi.edu
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