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PMID: 17369424 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

On the mechanism of TBA block of the TRPV1 channel.

Biophysical journal ·Vol. 92 ·No. 11 ·2007-06-01 ·Pages 3901-14

Oseguera AJ, Islas LD, García-Villegas R, Rosenbaum T

Abstract

The transient receptor potential vanilloid 1 (TRPV1) channel is a nonselective cation channel activated by capsaicin and responsible for thermosensation. To date, little is known about the gating characteristics of these channels. Here we used tetrabutylammonium (TBA) to determine whether this molecule behaves as an ion conduction blocker in TRPV1 channels and to gain insight into the nature of the activation gate of this protein. TBA belongs to a family of classic potassium channel blockers that have been widely used as tools for determining the localization of the activation gate and the properties of the pore of several ion channels. We found TBA to be a voltage-dependent pore blocker and that the properties of block are consistent with an open-state blocker, with the TBA molecule binding to multiple open states, each with different blocker affinities. Kinetics of channel closure and burst-length analysis in the presence of blocker are consistent with a state-dependent blocking mechanism, with TBA interfering with closing of an activation gate. This activation gate may be located cytoplasmically with respect to the binding site of TBA ions, similar to what has been observed in potassium channels. We propose an allosteric model for TRPV1 activation and block by TBA, which explains our experimental data.

MeSH Terms
Cell Line Detergents/pharmacology Humans Protein Structure, Tertiary Quaternary Ammonium Compounds/pharmacology TRPV Cation Channels/antagonists & inhibitors
Chemicals
Detergents Quaternary Ammonium Compounds TRPV Cation Channels TRPV1 protein, human tetrabutylammonium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Oseguera Andrés Jara
Departamento de Biofísica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México.
Islas León D
García-Villegas Refugio
Rosenbaum Tamara
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1529/biophysj.106.102400
Published
2007-06-01
Epub
2007-00-16
Pages
3901-14
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1868982
Subset
IM
External Links
PubMed source DOI: 10.1529/biophysj.106.102400 PMC Full Text View journal details
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