Tags

Type your tag names separated by a space and hit enter

A TRPA1-dependent mechanism for the pungent sensation of weak acids.
J Gen Physiol. 2011 Jun; 137(6):493-505.JG

Abstract

Acetic acid produces an irritating sensation that can be attributed to activation of nociceptors within the trigeminal ganglion that innervate the nasal or oral cavities. These sensory neurons sense a diverse array of noxious agents in the environment, allowing animals to actively avoid tissue damage. Although receptor mechanisms have been identified for many noxious chemicals, the mechanisms by which animals detect weak acids, such as acetic acid, are less well understood. Weak acids are only partially dissociated at neutral pH and, as such, some can cross the cell membrane, acidifying the cell cytosol. The nociceptor ion channel TRPA1 is activated by CO(2), through gating of the channel by intracellular protons, making it a candidate to more generally mediate sensory responses to weak acids. To test this possibility, we measured responses to weak acids from heterologously expressed TRPA1 channels and trigeminal neurons with patch clamp recording and Ca(2+) microfluorometry. Our results show that heterologously expressed TRPA1 currents can be induced by a series of weak organic acids, including acetic, propionic, formic, and lactic acid, but not by strong acids. Notably, the degree of channel activation was predicted by the degree of intracellular acidification produced by each acid, suggesting that intracellular protons are the proximate stimulus that gates the channel. Responses to weak acids produced a Ca(2+)-independent inactivation that precluded further activation by weak acids or reactive chemicals, whereas preactivation by reactive electrophiles sensitized TRPA1 channels to weak acids. Importantly, responses of trigeminal neurons to weak acids were highly overrepresented in the subpopulation of TRPA1-expressing neurons and were severely reduced in neurons from TRPA1 knockout mice. We conclude that TRPA1 is a general sensor for weak acids that produce intracellular acidification and suggest that it functions within the pain pathway to mediate sensitivity to cellular acidosis.

Authors+Show Affiliations

Department of Biological Sciences, Section of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21576376

Citation

Wang, Yuanyuan Y., et al. "A TRPA1-dependent Mechanism for the Pungent Sensation of Weak Acids." The Journal of General Physiology, vol. 137, no. 6, 2011, pp. 493-505.
Wang YY, Chang RB, Allgood SD, et al. A TRPA1-dependent mechanism for the pungent sensation of weak acids. J Gen Physiol. 2011;137(6):493-505.
Wang, Y. Y., Chang, R. B., Allgood, S. D., Silver, W. L., & Liman, E. R. (2011). A TRPA1-dependent mechanism for the pungent sensation of weak acids. The Journal of General Physiology, 137(6), 493-505. https://doi.org/10.1085/jgp.201110615
Wang YY, et al. A TRPA1-dependent Mechanism for the Pungent Sensation of Weak Acids. J Gen Physiol. 2011;137(6):493-505. PubMed PMID: 21576376.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A TRPA1-dependent mechanism for the pungent sensation of weak acids. AU - Wang,Yuanyuan Y, AU - Chang,Rui B, AU - Allgood,Sallie D, AU - Silver,Wayne L, AU - Liman,Emily R, Y1 - 2011/05/16/ PY - 2011/5/18/entrez PY - 2011/5/18/pubmed PY - 2011/10/5/medline SP - 493 EP - 505 JF - The Journal of general physiology JO - J Gen Physiol VL - 137 IS - 6 N2 - Acetic acid produces an irritating sensation that can be attributed to activation of nociceptors within the trigeminal ganglion that innervate the nasal or oral cavities. These sensory neurons sense a diverse array of noxious agents in the environment, allowing animals to actively avoid tissue damage. Although receptor mechanisms have been identified for many noxious chemicals, the mechanisms by which animals detect weak acids, such as acetic acid, are less well understood. Weak acids are only partially dissociated at neutral pH and, as such, some can cross the cell membrane, acidifying the cell cytosol. The nociceptor ion channel TRPA1 is activated by CO(2), through gating of the channel by intracellular protons, making it a candidate to more generally mediate sensory responses to weak acids. To test this possibility, we measured responses to weak acids from heterologously expressed TRPA1 channels and trigeminal neurons with patch clamp recording and Ca(2+) microfluorometry. Our results show that heterologously expressed TRPA1 currents can be induced by a series of weak organic acids, including acetic, propionic, formic, and lactic acid, but not by strong acids. Notably, the degree of channel activation was predicted by the degree of intracellular acidification produced by each acid, suggesting that intracellular protons are the proximate stimulus that gates the channel. Responses to weak acids produced a Ca(2+)-independent inactivation that precluded further activation by weak acids or reactive chemicals, whereas preactivation by reactive electrophiles sensitized TRPA1 channels to weak acids. Importantly, responses of trigeminal neurons to weak acids were highly overrepresented in the subpopulation of TRPA1-expressing neurons and were severely reduced in neurons from TRPA1 knockout mice. We conclude that TRPA1 is a general sensor for weak acids that produce intracellular acidification and suggest that it functions within the pain pathway to mediate sensitivity to cellular acidosis. SN - 1540-7748 UR - https://www.unboundmedicine.com/medline/citation/21576376/A_TRPA1_dependent_mechanism_for_the_pungent_sensation_of_weak_acids_ L2 - https://rupress.org/jgp/article-lookup/doi/10.1085/jgp.201110615 DB - PRIME DP - Unbound Medicine ER -