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TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons.
Neuroscience. 2017 06 14; 353:76-86.N

Abstract

The molecular sensor of innocuous (painless) cold sensation is well-established to be transient receptor potential cation channel, subfamily M, member 8 (TRPM8). However, the role of transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in noxious (painful) cold sensation has been controversial. We find that TRPA1 channels contribute to the noxious cold sensitivity of mouse somatosensory neurons, independent of TRPM8 channels, and that TRPA1-expressing neurons are largely non-overlapping with TRPM8-expressing neurons in mouse dorsal-root ganglia (DRG). However, relatively few TRPA1-expressing neurons (e.g., responsive to allyl isothiocyanate or AITC, a selective TRPA1 agonist) respond overtly to cold temperature in vitro, unlike TRPM8-expressing neurons, which almost all respond to cold. Using somatosensory neurons from TRPM8-/- mice and subtype-selective blockers of TRPM8 and TRPA1 channels, we demonstrate that responses to cold temperatures from TRPA1-expressing neurons are mediated by TRPA1 channels. We also identify two factors that affect the cold-sensitivity of TRPA1-expressing neurons: (1) cold-sensitive AITC-sensitive neurons express relatively more TRPA1 transcripts than cold-insensitive AITC-sensitive neurons and (2) voltage-gated potassium (KV) channels attenuate the cold-sensitivity of some TRPA1-expressing neurons. The combination of these two factors, combined with the relatively weak agonist-like activity of cold temperature on TRPA1 channels, partially explains why few TRPA1-expressing neurons respond to cold. Blocking KV channels also reveals another subclass of noxious cold-sensitive DRG neurons that do not express TRPM8 or TRPA1 channels. Altogether, the results of this study provide novel insights into the cold-sensitivity of different subclasses of somatosensory neurons.

Authors+Show Affiliations

Department of Biology, University of Utah, 257 S. 1400 E., Salt Lake City, UT 84112, United States.Department of Biology, University of Utah, 257 S. 1400 E., Salt Lake City, UT 84112, United States.Department of Biology, University of Utah, 257 S. 1400 E., Salt Lake City, UT 84112, United States.Department of Biology, University of Utah, 257 S. 1400 E., Salt Lake City, UT 84112, United States.Department of Biology, University of Utah, 257 S. 1400 E., Salt Lake City, UT 84112, United States. Electronic address: russ.teichert@utah.edu.

Pub Type(s)

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

Language

eng

PubMed ID

28408328

Citation

Memon, Tosifa, et al. "TRPA1 Expression Levels and Excitability Brake By KV Channels Influence Cold Sensitivity of TRPA1-expressing Neurons." Neuroscience, vol. 353, 2017, pp. 76-86.
Memon T, Chase K, Leavitt LS, et al. TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons. Neuroscience. 2017;353:76-86.
Memon, T., Chase, K., Leavitt, L. S., Olivera, B. M., & Teichert, R. W. (2017). TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons. Neuroscience, 353, 76-86. https://doi.org/10.1016/j.neuroscience.2017.04.001
Memon T, et al. TRPA1 Expression Levels and Excitability Brake By KV Channels Influence Cold Sensitivity of TRPA1-expressing Neurons. Neuroscience. 2017 06 14;353:76-86. PubMed PMID: 28408328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons. AU - Memon,Tosifa, AU - Chase,Kevin, AU - Leavitt,Lee S, AU - Olivera,Baldomero M, AU - Teichert,Russell W, Y1 - 2017/04/10/ PY - 2017/01/06/received PY - 2017/03/30/revised PY - 2017/04/01/accepted PY - 2017/4/15/pubmed PY - 2018/3/15/medline PY - 2017/4/15/entrez KW - K(V)1.2 KW - TRPA1 KW - TRPM8 KW - cold pain KW - ion channel KW - pharmacology SP - 76 EP - 86 JF - Neuroscience JO - Neuroscience VL - 353 N2 - The molecular sensor of innocuous (painless) cold sensation is well-established to be transient receptor potential cation channel, subfamily M, member 8 (TRPM8). However, the role of transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in noxious (painful) cold sensation has been controversial. We find that TRPA1 channels contribute to the noxious cold sensitivity of mouse somatosensory neurons, independent of TRPM8 channels, and that TRPA1-expressing neurons are largely non-overlapping with TRPM8-expressing neurons in mouse dorsal-root ganglia (DRG). However, relatively few TRPA1-expressing neurons (e.g., responsive to allyl isothiocyanate or AITC, a selective TRPA1 agonist) respond overtly to cold temperature in vitro, unlike TRPM8-expressing neurons, which almost all respond to cold. Using somatosensory neurons from TRPM8-/- mice and subtype-selective blockers of TRPM8 and TRPA1 channels, we demonstrate that responses to cold temperatures from TRPA1-expressing neurons are mediated by TRPA1 channels. We also identify two factors that affect the cold-sensitivity of TRPA1-expressing neurons: (1) cold-sensitive AITC-sensitive neurons express relatively more TRPA1 transcripts than cold-insensitive AITC-sensitive neurons and (2) voltage-gated potassium (KV) channels attenuate the cold-sensitivity of some TRPA1-expressing neurons. The combination of these two factors, combined with the relatively weak agonist-like activity of cold temperature on TRPA1 channels, partially explains why few TRPA1-expressing neurons respond to cold. Blocking KV channels also reveals another subclass of noxious cold-sensitive DRG neurons that do not express TRPM8 or TRPA1 channels. Altogether, the results of this study provide novel insights into the cold-sensitivity of different subclasses of somatosensory neurons. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/28408328/TRPA1_expression_levels_and_excitability_brake_by_KV_channels_influence_cold_sensitivity_of_TRPA1_expressing_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(17)30240-3 DB - PRIME DP - Unbound Medicine ER -