ArticlePflugers Archiv : European journal of physiology2014
Bimodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal strong intrinsic voltage-dependent inactivation.
Article in Pflugers Archiv : European journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- The Contact Allergen Methylisothiazolinone (MIT) is a Potent Activator of the TRPA1 Ion Channel.Pharmacology research & perspectives · 2025Article
- Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes.Nature neuroscience · 2022Article
- Transient receptor potential ankyrin 1 channel: An evolutionarily tuned thermosensor.Physiological research · 2021Review
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- Voltage-dependent modulation of TRPA1 currents by diphenhydramine.Cell calcium · 2020Article
- KCa1.1 channels regulate βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Protein Kinase C Mediates the Corticosterone-induced Sensitization of Dorsal Root Ganglion Neurons Innervating the Rat Stomach.Journal of neurogastroenterology and motility · 2017Article
- Agonist-induced sensitisation of the irritant receptor ion channel TRPA1.The Journal of physiology · 2016Article
- N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel.Scientific reports · 2016Article
- Naturally Produced Defensive Alkenal Compounds Activate TRPA1.Chemical senses · 2016Article
- Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable'.Bioscience reports · 2015Article
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Transient receptor potential A1 (TRPA1) is implicated in somatosensory processing and pathological pain sensation. Although not strictly voltage-gated, ionic currents of TRPA1 typically rectify outwardly, indicating channel activation at depolarized membrane potentials. However, some reports also showed TRPA1 inactivation at high positive potentials, implicating voltage-dependent inactivation. Here we report a conserved leucine residue, L906, in the putative pore helix, which strongly impacts the voltage dependency of TRPA1. Mutation of the leucine to cysteine (L906C) converted the channel from outward to inward rectification independent of divalent cations and irrespective to stimulation by allyl isothiocyanate. The mutant, but not the wild-type channel, displayed exclusively voltage-dependent inactivation at positive potentials. The L906C mutation also exhibited reduced sensitivity to inhibition by TRPA1 blockers, HC030031 and ruthenium red. Further mutagenesis of the leucine to all natural amino acids individually revealed that most substitutions at L906 (15/19) resulted in inward rectification, with exceptions of three amino acids that dramatically reduced channel activity and one, methionine, which mimicked the wild-type channel. Our data are plausibly explained by a bimodal gating model involving both voltage-dependent activation and inactivation of TRPA1. We propose that the key pore helix residue, L906, plays an essential role in responding to the voltage-dependent gating.
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