The conducting state of TRPA1 modulates channel lateral mobility

• Published in: Cell calcium (Edinburgh) Vol. 116; p. 102800
• Main Authors: Sampieri, Alicia, Padilla-Flores, Teresa, Thawani, Aditya R., Lam, Pui-Ying, Fuchter, Matthew J., Peterson, Randall, Vaca, Luis
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2023
• Subjects: Allyl isothiocyanate; Animals; Cholesterol; Electrophysiological Phenomena; Lateral mobility; Transient Receptor Potential Channels - metabolism; TRPA1 Cation Channel; TRPA1 channel; TRPswitch; Zebrafish - metabolism; TRPA1 channel; Allyl isothiocyanate; Lateral mobility; TRPswitch; Cholesterol
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2023.102800

•Two chemical agonists of TRPA1 with different activation mechanisms induced a drastic reduction on channel lateral mobility.•An inverse correlation was found between channel open probability and lateral mobility.•Deactivation of TRPswitch B, a photoswitchable chemical agonists of TRPA1 restores lateral mobility to basal levels.•Cholesterol reduction at the plasma membrane prevents the reduction of lateral mobility induced by the chemical agonists and reduced channel open probability.•These results suggest that the conducting state of TRPA1 modulates lateral mobility of the channel at the plasma membrane. We have studied Danio rerio (Zebrafish) TRPA1 channel using a method that combines single channel electrophysiological and optical recordings to evaluate lateral mobility and channel gating simultaneously in single channels. TRPA1 channel activation by two distinct chemical ligands: allyl isothiocyanate (AITC) and TRPswitch B, results in substantial reduction of channel lateral mobility at the plasma membrane. Incubation with the cholesterol sequestering agent methyl-β-cyclodextrin (MβCD), prevents the reduction on lateral mobility induced by the two chemical agonists. This results strongly suggest that the open conformation of TRPA1 modulates channel lateral mobility probably by facilitating the insertion of the channel into cholesterol-enriched domains at the plasma membrane. [Display omitted]