Figure 1

Histidine substitution at D918 in TRPA1 generates a high affinity Zn²⁺ inhibitory site. (A,D) Effect of extracellular Zn²⁺ on TRPA1 currents in HEK 293 cells transfected with WT or D918H TRPA1 channels. TRPA1 current was elicited by exposure to cinnamaldehyde (100 µM). The membrane potential was held at −80 mV and ramped (−80 mV to +80 mV, 1 V/s) once every second. (B,E) The I-V relationships of currents shown at indicated time points. Zn²⁺ potentiates the WT current and blocks D918H currents. (C) The structure of human TRPA1 modified from published data on National Center for Biotechnology Information (NCBI), showing a side view of the S5~S6 transmembrane domains from two opposing subunits in a TRPA1 channel. The backbones of D915 residues (homologous with rat TRPA1 D918) are highlighted. (F) Average data from experiments as in A,D showing the magnitude of the currents in the presence of Zn²⁺, at the concentration indicated, relative to the starting current level I_Zn2+/I_initial (measured at +80 mV). ****P < 0.0001 (Sidak’s multiple comparison following two-way ANOVA); N ≥ 4.