TRPA1 | Transient Receptor Potential Cation Channel Subfamily A Member 1

Family:
Transient  receptor potential channels

Subgroups:
TRPC (TRPC1–TRPC7), TRPV (TRPV1-TRPV6), TRPA1, TRPM (TRPM1–TRPM8), TRPP (TRPP1–TRPP3, PKD1, PKDREJ, PKDL1–PKDL3), TRPML (TRPML1–TRPML3), TRPN

Topology:
Most TRP channels are composed of 6 transmembrane domains (helices) with intracellular N- and C-termini, non-selectively permeable to various cations

TRPA1: Background information

TRPA1, also known as transient receptor potential ankyrin 1 and ANKTM1, is an ion channel best known as sensor for environmental irritants giving rise to somatosensory modalities such as pain, cold and itch. TRPA1 contains 14 N-terminal ankyrin repeats and is believed to function as a mechanical and chemical stress sensor. Studies indicate that the function may involve a role in signal transduction, growth control and as chemosensor. TRPA1 is considered as an attractive pain target as it has a central role in the pain response to endogenous inflammatory mediators.

Gene:
TRPA1

Human Protein:
UniProt O75762

Tissue:
Peripheral sensory neurons, hair cells, nociceptive neurons, human fibroblasts, liposarcoma cells,

Function/ Application:
Detection of chemical stimulus in sensory perception of pain, temperature transducer for ‘‘cold’’, nociceptive transduction, inflammation, inner ear function, calcium ion transmembrane transport

Pathology:
Episodic pain syndrome, familial, 1 (FEPS1), hyperalgesia, asthma, dentin sensitivity, somatoform disorder

Interaction:
AITC, HC030031, TMEM100, bradykinin, CYLD, SCMA, A-967079, PH domain and leucine rich repeat protein phosphatase 1, Phosphoribosylglycinamide formyltransferase

Modulator:
Gingerol, allicin, gentamycin, eugenol, cinnamaldehyde, mustard oil, menthol, delta 9-tetrahydrocannabinol (THC), ruthetium red

Assays:
Patch Clamp: whole cell, extracellular perfusion

Particularities:
Ligand-gated as well as mechano-sensitive ion channel

Recommended Reviews:
International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels., Pharmacol Rev 55(4):591-6 Clapham, et al. 2003 

Data and Applications

TRPA1 - Temperature Dependency

Icon Orbit Mini   Orbit mini data and applications:

Orbit Mini TRPA1

(A) Effect of temperature on TRPA1 activity
(B) The open probability (Po) versus the temperature and fitted with Boltzmann equation (EC50 was found at 14˚C).

The Arrhenius plot of the same data resulted in a Q10 of 46 (Literature: Q10 ~ 40).

TRPA1 - Inhibition by A967079 and AMG0902

TRPA1 Inhibition SP384icon sp96   SyncroPatch 384i (a predecessor model of the SyncroPatch 384) data and applications: 
Cells were kindly provided by AcCELLerate.

Inhibition of TRPA1 by A967079 and AMG0902. A TRPA1-mediated responses were blocked by A967079 in a concentration-dependent manner with an IC50 value (12.4 nM) in good agreement with the literature value of 50 nM. B TRPA1-mediated responses were blocked by AMG0902 in a concentration-dependent manner with an IC50 value of 48 nM (n = 349) in good agreement with the literature value of 68 nM.

 

TRPA1 - Current Traces

TRPA1 Screenshoticon pl   Patchliner data and applications: 
Cells were kindly supplied by Millipore.

Shown is a screenshot from a recording on a 4-channel Patchliner from HEK293 cells expressing TRPA1. Currents were activated by ca. 20 s application of 3 μM AITC followed by wash out. On the left raw whole cell currents as responses to 0.2 s voltage ramps (−100 mV to +100 mV) which were applied every 10 s are shown. On the right currents at +95 mV are plotted against time.

TRPA1 - Current Time Course

TRPA1 Patchlinericon pl   Patchliner data and applications:
Cells were kindly supplied by Millipore.

Shown is the time course of the current measured at +95 mV from an individual cell. The legend indicates the time periods in which the activator AITC was applied. Here we demonstrate the reproducibility of the current responses for TRPA1.

TRPA1 - Activation by carvacrol

TRPA1 Carvacrol SP384iicon sp96   SyncroPatch 384i (a predecessor model of the SyncroPatch 384) data and applications: 
Cells were kindly provided by AcCELLerate.

Activation of TRPA1 expressed in CHO cell on the SyncroPatch 384i (a predecessor model of the SyncroPatch 384). A Screenshot of the PatchControl 384 software depicts raw data traces of TRPA1- expressing CHO cells as recorded on one NPC-384 patch clamp chip (4 holes). A single concentration of carvacrol was added to each well and the concentration response curve calculated across the plate. B Average CRC (left) for carvacrol for n = 355 wells and average traces (right). TRPA1 was robustly activated by carvacrol. At higher concentrations (above 400 µM) desensitization of the channel was observed (tachyphylaxis) which resulted in smaller amplitudes upon repeated application.

Webinars

27.01.2016 | Webinar: Instant bilayers - just add protein

Icon Orbit   Orbit 16 and   Icon Orbit Mini   Orbit Mini

Orbits V1 flat 250pxThis webinar covers the use of the lipid bilayer platforms from Nanion: the Orbit16 and the Orbit mini for characterization of membrane proteins like ion channels, bacterial porins and biological nanopores. Both bilayer systems support high quality low noise recordings, but differ in throughput capabilities and experimental features. The Orbit16, introduced in 2012 is a device for efficient formation of 16 lipid bilayers simultaneously, allowing for parallel bilayer-reconstitution of ion channels and nanopores.

 

07.10.2015 | Webinar: Patch Clamp Made Easy, Fast Track to Excellence

icon pap   Port-a-Patch

This webinar shows applications that go way beyond possibilities of conventional patch-clamping, where the Port-a-Patch facilitates completely novel scientific directions.

Posters

2021 - Activation and inhibition of assay-ready TRPA1 and TRPV cells: an automated patch clamp study

icon pap Port-a-Patch, icon pl   Patchliner and   icon sp96  SyncroPatch 384i (a predecessor model of SyncroPatch 384) Biophysical Society Meeting 2021  logo pdf   (1.5MB)

2016 - Next level toxicity screening: From single channel to overall cell behavior

Icon Orbit Mini   Orbit mini,   Icon CE   CardioExcyte 96 and   icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) poster, Meeting of the French Society of Toxinology (SFET) 2015  logo pdf   (0.9 MB)

2015 - The backstage pass to study your favorite TRP channel

icon pap   Port-a-Patch and   icon pl   Patchliner and   icon sp96   SyncroPatch 384PE  (a predecessor model of the SyncroPatch 384) poster, TRP Meeting 2015   logo pdf   (2.2 MB)

Application Notes

TRPA1 - "TRPA1 activation by allyl isothiocyanate recorded on the Port-a-Patch"

icon pap   Port-a-Patch application note:  logo pdf   (1.4 MB)

TRPA1 - "High Throughput Activation and Block of hTRPA1 on Nanion’s SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) application note   logo pdf   (0.6 MB)
Cells were kindly provided by Millipore.

hTRPA1 - "Reproducible activation and pharmacology of hTRPA1 on the SyncroPatch 384"

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384) application note:   logo pdf   (3.1 MB)
Cells were kindly provided by Charles River

Publications

2021 - The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain

icon vpp  Vesicle Prep Pro and icon pap Port-a-Patch Pre-Print Publication in BioRxiv (2021)

Authors:
Moparthi L., Sinica V., Filipovic M., Vlachova V., Zygmunt P.M.

2021 - The Agonist Action of Alkylphenols on TRPA1 Relates to Their Effects on Membrane Lipid Order: Implications for TRPA1-Mediated Chemosensation

icon pl  Patchliner Publication in International Journal of Molecular Sciences (2021)

Authors:
Startek J.B., Milici A., Naert R., Segal A., Alpizar Y.A., Voets T., Talavera K.

2020 - New natural agonists of the transient receptor potential Ankyrin 1 (TRPA1) channel

icon pap   Port-a-Patch publication in Nature Scientific Reports (2020)

Authors:
Legrand C., Merlini J.M., de Senarclens‑Bezençon C., Michlig S.

2020 - Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel

icon pap  Port-a-Patch and   icon vpp   Vesicle Prep Pro publication in Cell Calcium (2020)

Authors: 
Moparthi L., Zygmunt P.M.

2020 - Calcium activates purified human TRPA1 with and without its N-terminal ankyrin repeat domain in the absence of calmodulin

icon pap   Port-a-Patch and   icon vpp   Vesicle Prep Pro publication in Cell Calcium (2020)

Authors: 
Moparthi L., Moparthi S.B., Wenger J., Zygmunt P.M.

2018 - Differential interactions of bacterial lipopolysaccharides with lipid membranes: implications for TRPA1-mediated chemosensation

icon vpp   Vesicle Prep Pro publication in Scientific Reports (2018)

Authors:
Startek J.B., Talavera K., Voets T., Alpizar Y.A.

2016 - The N-terminal Ankyrin Repeat Domain Is Not Required for Electrophile and Heat Activation of the Purified Mosquito TRPA1 Receptor

icon pap  Port-a-Patch and   icon vpp   Vesicle Prep Pro publication in Nature (2016)

Authors: 
Survery S., Moparthi L., Kjellbom P., Högestätt E.D., Zygmunt P.M., Johanson U.

2016 - Photosensitization in Porphyrias and Photodynamic Therapy Involves TRPA1 and TRPV1

icon pap  Port-a-Patch and   icon vpp   Vesicle Prep Pro publication in The Journal of Neuroscience (2016)

Authors: 
Babes A., Sauer S.K., Moparthi L., Kichko T.I., Neacsu C., Namer B., Filipovic M., Zygmunt P.M., Reeh P.W., Fischer M.J.

2016 - Human TRPA1 is a heat sensor displaying intrinsic U-shaped thermosensitivity

icon pap  Port-a-Patch and   icon vpp   Vesicle Prep Pro publication in Scientific Reports (2016)

Authors: 
Moparthi L., Kichko T. I., Eberhardt M., Högestätt E. D., Kjellbom P., Johanson U., Reeh P., W., Leffler A., Filipovic M. R., Zygmunt P. M.

2014 - Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain

icon pap  Port-a-Patch and   icon vpp   Vesicle Prep Pro publication in Proceedings of the National Academy of Sciences of the United States of America (2014)

Authors: 
Moparthi L., Survery S., Kreir M., Simonsen C., Kjellbom P., Högestätt E.D., Johanson U., Zygmunt P.M.

2014 - Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells

icon pap  Port-a-Patch publication in Cellular Signalling (2014)

Authors:
Mergler S., Derckx R., Reinach P.S., Garreis F., Böhm A., Schmelzer L., Skosyrski S., Ramesh N., Abdelmessih S., Polat O.K., Khajavi N., Riechardt A.I.

2012 - TRPA1 Agonist Activity of Probenecid Desensitizes Channel Responses: Consequences for Screening

icon pl   Patchliner publication in ASSAY and Drug Development Technologies (2012)

Authors: 
McClenaghan C., Zeng F., Verkuyl J.M.

2009 - Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases

icon pap  Port-a-Patch publication in FASEB (2009)

Authors:
Bessac B.F., Sivula M., von Hehn C.A., Caceres A.I., Escalera, J, Jordt S.

2008 - TRPA1 is a major oxidant sensor in murine airway sensory neurons

icon pap  Port-a-Patch publication in The Journal of Clinical Investigation (2008)

Authors: 
Bessac B.F., Sivula M., von Hehn C.A., Escalera J., Cohn L., Jordt S.E.

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