Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes

Ricardo E Rivera-Acevedo; Stephan A Pless; Stephan K W Schwarz; Christopher A Ahern

doi:10.1124/mol.112.079277

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Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes

Journal article

Peer reviewed

Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes

Ricardo E Rivera-Acevedo, Stephan A Pless, Stephan K W Schwarz and Christopher A Ahern

Molecular pharmacology, Vol.82(6), pp.1129-1135

12/2012

DOI: 10.1124/mol.112.079277

PMID: 22956771

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Abstract

Transient receptor potential vanilloid subtype 1 (TRPV1) channels are essential nociceptive integrators in primary afferent neurons. These nonselective cation channels are inhibited by local anesthetic compounds through an undefined mechanism. Here, we show that lidocaine inhibits TRPV1 channels expressed in Xenopus laevis oocytes, whereas the neutral local anesthetic, benzocaine, does not, suggesting that a titratable amine is required for high-affinity inhibition. Consistent with this possibility, extracellular tetraethylammonium (TEA) and tetramethylammonium application produces potent, voltage-dependent pore block. Alanine substitutions at Phe649 and Glu648, residues in the putative TRPV1 pore region, significantly abrogated the concentration-dependent TEA inhibition. The results suggest that large cations, shown previously to enter cells through activated transient receptor potential channels, can also act as channel blockers.

Lidocaine - pharmacology

Tetraethylammonium - pharmacology

Xenopus Proteins - genetics

Capsaicin - pharmacology

Oocytes - metabolism

Xenopus laevis

Benzocaine - pharmacology

Anesthetics, Local - pharmacology

TRPV Cation Channels - genetics

Xenopus Proteins - antagonists & inhibitors

TRPV Cation Channels - metabolism

Animals

Mutation - drug effects

TRPV Cation Channels - biosynthesis

TRPV Cation Channels - antagonists & inhibitors

Oocytes - drug effects

Xenopus Proteins - biosynthesis

Xenopus Proteins - metabolism

Quaternary Ammonium Compounds - pharmacology

Details

Title: Subtitle: Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes
Creators: Ricardo E Rivera-Acevedo - Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada
Stephan A Pless
Stephan K W Schwarz
Christopher A Ahern
Resource Type: Journal article
Publication Details: Molecular pharmacology, Vol.82(6), pp.1129-1135
Publisher: United States
DOI: 10.1124/mol.112.079277
PMID: 22956771
ISSN: 0026-895X
eISSN: 1521-0111
Grant note: Canadian Institutes of Health Research R24 NS104617 / NINDS NIH HHS
Language: English
Date published: 12/2012
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984070290602771

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