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Activation characteristics of transient receptor potential ankyrin 1 and its role in nociception.
Am J Physiol Cell Physiol. 2011 Sep; 301(3):C587-600.AJ

Abstract

Transient receptor potential (TRP) ankyrin 1 (TRPA1) is a Ca(2+)-permeant, nonselective cationic channel. It is predominantly expressed in the C afferent sensory nerve fibers of trigeminal and dorsal root ganglion neurons and is highly coexpressed with the nociceptive ion channel transient receptor potential vanilloid 1 (TRPV1). Several physical and chemical stimuli have been shown to activate the channel. In this study, we have used electrophysiological techniques and behavioral models to characterize the properties of TRPA1. Whole cell TRPA1 currents induced by brief application of lower concentrations of N-methyl maleimide (NMM) or allyl isothiocyanate (AITC) can be reversed readily by washout, whereas continuous application of higher concentrations of NMM or AITC completely desensitized the currents. The deactivation and desensitization kinetics differed between NMM and AITC. TRPA1 current amplitude increased with repeated application of lower concentrations of AITC, whereas saturating concentrations of AITC induced tachyphylaxis, which was more pronounced in the presence of extracellular Ca(2+). The outward rectification exhibited by native TRPA1-mediated whole cell and single-channel currents was minimal as compared with other TRP channels. TRPA1 currents were negatively modulated by protons and polyamines, both of which activate the heat-sensitive channel, TRPV1. Interestingly, neither protein kinase C nor protein kinase A activation sensitized AITC-induced currents, but each profoundly sensitized capsaicin-induced currents. Current-clamp experiments revealed that AITC produced a slow and sustained depolarization as compared with capsaicin. TRPA1 is also expressed at the central terminals of nociceptors at the caudal spinal trigeminal nucleus. Activation of TRPA1 in this area increases the frequency and amplitude of miniature excitatory or inhibitory postsynaptic currents. In behavioral studies, intraplantar and intrathecal administration of AITC induced more pronounced and prolonged changes in nociceptive behavior than those induced by capsaicin. In conclusion, the characteristics of TRPA1 we have delineated suggest that it might play a unique role in nociception.

Authors+Show Affiliations

Dept. of Pharmacology, Southern Illinois Univ. School of Medicine, Springfield, IL 62702, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

21653898

Citation

Raisinghani, Manish, et al. "Activation Characteristics of Transient Receptor Potential Ankyrin 1 and Its Role in Nociception." American Journal of Physiology. Cell Physiology, vol. 301, no. 3, 2011, pp. C587-600.
Raisinghani M, Zhong L, Jeffry JA, et al. Activation characteristics of transient receptor potential ankyrin 1 and its role in nociception. Am J Physiol Cell Physiol. 2011;301(3):C587-600.
Raisinghani, M., Zhong, L., Jeffry, J. A., Bishnoi, M., Pabbidi, R. M., Pimentel, F., Cao, D. S., Evans, M. S., & Premkumar, L. S. (2011). Activation characteristics of transient receptor potential ankyrin 1 and its role in nociception. American Journal of Physiology. Cell Physiology, 301(3), C587-600. https://doi.org/10.1152/ajpcell.00465.2010
Raisinghani M, et al. Activation Characteristics of Transient Receptor Potential Ankyrin 1 and Its Role in Nociception. Am J Physiol Cell Physiol. 2011;301(3):C587-600. PubMed PMID: 21653898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation characteristics of transient receptor potential ankyrin 1 and its role in nociception. AU - Raisinghani,Manish, AU - Zhong,Linlin, AU - Jeffry,Joseph A, AU - Bishnoi,Mahendra, AU - Pabbidi,Reddy M, AU - Pimentel,Fátima, AU - Cao,De-Shou, AU - Evans,M Steven, AU - Premkumar,Louis S, Y1 - 2011/06/08/ PY - 2011/6/10/entrez PY - 2011/6/10/pubmed PY - 2012/1/5/medline SP - C587 EP - 600 JF - American journal of physiology. Cell physiology JO - Am J Physiol Cell Physiol VL - 301 IS - 3 N2 - Transient receptor potential (TRP) ankyrin 1 (TRPA1) is a Ca(2+)-permeant, nonselective cationic channel. It is predominantly expressed in the C afferent sensory nerve fibers of trigeminal and dorsal root ganglion neurons and is highly coexpressed with the nociceptive ion channel transient receptor potential vanilloid 1 (TRPV1). Several physical and chemical stimuli have been shown to activate the channel. In this study, we have used electrophysiological techniques and behavioral models to characterize the properties of TRPA1. Whole cell TRPA1 currents induced by brief application of lower concentrations of N-methyl maleimide (NMM) or allyl isothiocyanate (AITC) can be reversed readily by washout, whereas continuous application of higher concentrations of NMM or AITC completely desensitized the currents. The deactivation and desensitization kinetics differed between NMM and AITC. TRPA1 current amplitude increased with repeated application of lower concentrations of AITC, whereas saturating concentrations of AITC induced tachyphylaxis, which was more pronounced in the presence of extracellular Ca(2+). The outward rectification exhibited by native TRPA1-mediated whole cell and single-channel currents was minimal as compared with other TRP channels. TRPA1 currents were negatively modulated by protons and polyamines, both of which activate the heat-sensitive channel, TRPV1. Interestingly, neither protein kinase C nor protein kinase A activation sensitized AITC-induced currents, but each profoundly sensitized capsaicin-induced currents. Current-clamp experiments revealed that AITC produced a slow and sustained depolarization as compared with capsaicin. TRPA1 is also expressed at the central terminals of nociceptors at the caudal spinal trigeminal nucleus. Activation of TRPA1 in this area increases the frequency and amplitude of miniature excitatory or inhibitory postsynaptic currents. In behavioral studies, intraplantar and intrathecal administration of AITC induced more pronounced and prolonged changes in nociceptive behavior than those induced by capsaicin. In conclusion, the characteristics of TRPA1 we have delineated suggest that it might play a unique role in nociception. SN - 1522-1563 UR - https://www.unboundmedicine.com/medline/citation/21653898/Activation_characteristics_of_transient_receptor_potential_ankyrin_1_and_its_role_in_nociception_ L2 - https://journals.physiology.org/doi/10.1152/ajpcell.00465.2010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -