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Am J Physiol Cell Physiol
2011 Sep 01;3013:C587-600. doi: 10.1152/ajpcell.00465.2010.
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Activation characteristics of transient receptor potential ankyrin 1 and its role in nociception.
Raisinghani M
,
Zhong L
,
Jeffry JA
,
Bishnoi M
,
Pabbidi RM
,
Pimentel F
,
Cao DS
,
Evans MS
,
Premkumar LS
.
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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.
Ahern,
Polyamines are potent ligands for the capsaicin receptor TRPV1.
2006, Pubmed,
Xenbase
Ahern,
Polyamines are potent ligands for the capsaicin receptor TRPV1.
2006,
Pubmed
,
Xenbase
Akopian,
Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization.
2007,
Pubmed
Andersson,
Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress.
2008,
Pubmed
Ashina,
Plasma levels of calcitonin gene-related peptide in chronic tension-type headache.
2000,
Pubmed
Babes,
Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor.
2004,
Pubmed
Bandell,
Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.
2004,
Pubmed
Bautista,
Pungent products from garlic activate the sensory ion channel TRPA1.
2005,
Pubmed
Bautista,
TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.
2006,
Pubmed
Bessac,
TRPA1 is a major oxidant sensor in murine airway sensory neurons.
2008,
Pubmed
Bhave,
cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation.
2002,
Pubmed
Bishnoi,
Possible consequences of blocking transient receptor potential vanilloid.
2011,
Pubmed
Bishnoi,
Preservation of acute pain and efferent functions following intrathecal resiniferatoxin-induced analgesia in rats.
2011,
Pubmed
Cesare,
Ion channels gated by heat.
1999,
Pubmed
Cesare,
Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat.
1999,
Pubmed
Corey,
TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells.
2004,
Pubmed
Doerner,
Transient receptor potential channel A1 is directly gated by calcium ions.
2007,
Pubmed
Everaerts,
The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil.
2011,
Pubmed
Goadsby,
The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats.
1993,
Pubmed
Grudt,
mu-Opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat.
1994,
Pubmed
Gupta,
Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries.
2007,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Hinman,
TRP channel activation by reversible covalent modification.
2006,
Pubmed
Jaquemar,
An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts.
1999,
Pubmed
Jeffry,
Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal cord for long lasting analgesia.
2009,
Pubmed
Jeske,
Cannabinoid WIN 55,212-2 regulates TRPV1 phosphorylation in sensory neurons.
2006,
Pubmed
Jordt,
Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.
2004,
Pubmed
Katsura,
Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats.
2006,
Pubmed
Kerstein,
Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors.
2009,
Pubmed
Khasar,
A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice.
1999,
Pubmed
Kim,
Expression of transient receptor potential ankyrin 1 (TRPA1) in the rat trigeminal sensory afferents and spinal dorsal horn.
2010,
Pubmed
Klionsky,
Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists.
2007,
Pubmed
Kobayashi,
Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors.
2005,
Pubmed
Kosugi,
Activation of TRPA1 channel facilitates excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord.
2007,
Pubmed
Kwan,
TRPA1 modulates mechanotransduction in cutaneous sensory neurons.
2009,
Pubmed
Kwan,
TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction.
2006,
Pubmed
Lassen,
CGRP may play a causative role in migraine.
2002,
Pubmed
Lopshire,
The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: whole-cell and single-channel studies.
1998,
Pubmed
Macpherson,
The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin.
2005,
Pubmed
Macpherson,
Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines.
2007,
Pubmed
Mishra,
TRPV1-lineage neurons are required for thermal sensation.
2011,
Pubmed
Mohapatra,
Desensitization of capsaicin-activated currents in the vanilloid receptor TRPV1 is decreased by the cyclic AMP-dependent protein kinase pathway.
2003,
Pubmed
Nagata,
Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing.
2005,
Pubmed
Nakatsuka,
Activation of central terminal vanilloid receptor-1 receptors and alpha beta-methylene-ATP-sensitive P2X receptors reveals a converged synaptic activity onto the deep dorsal horn neurons of the spinal cord.
2002,
Pubmed
Numazaki,
Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues.
2002,
Pubmed
Obata,
TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury.
2005,
Pubmed
Peier,
A TRP channel that senses cold stimuli and menthol.
2002,
Pubmed
Premkumar,
Targeting TRPV1 as an alternative approach to narcotic analgesics to treat chronic pain conditions.
2010,
Pubmed
Premkumar,
TRPV1: a target for next generation analgesics.
2008,
Pubmed
Premkumar,
Single-channel properties of native and cloned rat vanilloid receptors.
2002,
Pubmed
,
Xenbase
Premkumar,
Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation.
2005,
Pubmed
,
Xenbase
Premkumar,
Induction of vanilloid receptor channel activity by protein kinase C.
,
Pubmed
,
Xenbase
Premkumar,
Nociceptors in cardiovascular functions: complex interplay as a result of cyclooxygenase inhibition.
2006,
Pubmed
Raisinghani,
Activation of transient receptor potential vanilloid 1 (TRPV1) by resiniferatoxin.
2005,
Pubmed
,
Xenbase
Ro,
Activation of TRPV1 and TRPA1 leads to muscle nociception and mechanical hyperalgesia.
2009,
Pubmed
Rosenzweig,
The Drosophila ortholog of vertebrate TRPA1 regulates thermotaxis.
2005,
Pubmed
Salas,
TRPA1-mediated responses in trigeminal sensory neurons: interaction between TRPA1 and TRPV1.
2009,
Pubmed
Schmidt,
Nociceptive signals induce trafficking of TRPA1 to the plasma membrane.
2009,
Pubmed
Sikand,
Potentiation of glutamatergic synaptic transmission by protein kinase C-mediated sensitization of TRPV1 at the first sensory synapse.
2007,
Pubmed
Sotomayor,
In search of the hair-cell gating spring elastic properties of ankyrin and cadherin repeats.
2005,
Pubmed
Staruschenko,
Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel.
2010,
Pubmed
Story,
ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures.
2003,
Pubmed
Strecker,
Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice.
2005,
Pubmed
Wang,
Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain.
2008,
Pubmed
Wang,
Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission.
2005,
Pubmed
Zurborg,
Direct activation of the ion channel TRPA1 by Ca2+.
2007,
Pubmed
