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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes. / Rivera-Acevedo, Ricardo E; Pless, Stephan Alexander; Schwarz, Stephan K W; Ahern, Christopher A.

In: Molecular Pharmacology, Vol. 82, No. 6, 12.2012, p. 1129-35.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rivera-Acevedo, RE, Pless, SA, Schwarz, SKW & Ahern, CA 2012, 'Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes', Molecular Pharmacology, vol. 82, no. 6, pp. 1129-35. https://doi.org/10.1124/mol.112.079277

APA

Rivera-Acevedo, R. E., Pless, S. A., Schwarz, S. K. W., & Ahern, C. A. (2012). Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes. Molecular Pharmacology, 82(6), 1129-35. https://doi.org/10.1124/mol.112.079277

Vancouver

Rivera-Acevedo RE, Pless SA, Schwarz SKW, Ahern CA. Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes. Molecular Pharmacology. 2012 Dec;82(6):1129-35. https://doi.org/10.1124/mol.112.079277

Author

Rivera-Acevedo, Ricardo E ; Pless, Stephan Alexander ; Schwarz, Stephan K W ; Ahern, Christopher A. / Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes. In: Molecular Pharmacology. 2012 ; Vol. 82, No. 6. pp. 1129-35.

Bibtex

@article{3e266e1f0e644903bf73e1dffc64f5f5,
title = "Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes",
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.",
keywords = "Anesthetics, Local, Animals, Benzocaine, Capsaicin, Lidocaine, Mutation, Oocytes, Quaternary Ammonium Compounds, TRPV Cation Channels, Tetraethylammonium, Xenopus Proteins, Xenopus laevis",
author = "Rivera-Acevedo, {Ricardo E} and Pless, {Stephan Alexander} and Schwarz, {Stephan K W} and Ahern, {Christopher A}",
year = "2012",
month = dec,
doi = "10.1124/mol.112.079277",
language = "English",
volume = "82",
pages = "1129--35",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "6",

}

RIS

TY - JOUR

T1 - Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes

AU - Rivera-Acevedo, Ricardo E

AU - Pless, Stephan Alexander

AU - Schwarz, Stephan K W

AU - Ahern, Christopher A

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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.

KW - Anesthetics, Local

KW - Animals

KW - Benzocaine

KW - Capsaicin

KW - Lidocaine

KW - Mutation

KW - Oocytes

KW - Quaternary Ammonium Compounds

KW - TRPV Cation Channels

KW - Tetraethylammonium

KW - Xenopus Proteins

KW - Xenopus laevis

U2 - 10.1124/mol.112.079277

DO - 10.1124/mol.112.079277

M3 - Journal article

C2 - 22956771

VL - 82

SP - 1129

EP - 1135

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 6

ER -

ID: 122597586