Functional expression of TRPA1 cation channels in vestibular type II hair cells

Ingo Sparrer, Thien An Duong Dinh, Eberhard Jüngling, Martin Westhofen, Andreas Lückhoff
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Although the expression of TRPA1 proteins has been demonstrated in hair cells of the inner ear, the role of this Ca2+-permeable cation channel is unclear because TRPA1 knock-out mice have normal transduction currents in hair cells and do not show hearing impairment or vestibular problems. To test whether TRPA1 expression leads to the formation of intact ion channels in the plasma membrane of vestibular type II hair cells in the guinea pig, we measured whole-cell currents before and after stimulation with the specific agonists of TRPA1, allylisothiocyanate (AITC, 200 – 400 µM) and 3'-carbamoylbiphenyl-3-yl cyclohexylcarbamate (URB597, 100 µM). AITC induced currents with the typical current-voltage relation of TRPA1, as found in heterologous expression models. Currents densities reached maxima 168 ± 22 pA/pF (n = 41) at a holding potential of +60 mV and -62 ± 16 pA/pF at -60 mV. Current kinetics were characterized by an initial increase in amplitude over about 60 s, a subsequent plateau, and a complete current decline after wash-out of the drug. Repeated stimulations were possible. In the presence of URB597, similar currents developed but showed rapid desensitization under ongoing stimulation. We conclude that there is functional expression of TRPA1 in vestibular hair cells, at a current density relatively small in comparison to voltage gated currents. Thus, TRPA1 currents may modulate the electrical responses of hair cells. This may be relevant as potential side effects of many drugs and substances known to be activators of the polymodal channels TRPA1.