Publikationsdatenbank

A truly promiscuous channel:
D-menthol, L-menthol and the conductance of TRPV3 to NH4+ (2021)

Art

Poster

Autoren

Liebe, Hendrik (WE 2)

Liebe, Franziska (WE 2)

Manz, Gisela (WE 2)

Sponder, Gerhard (WE 2)

Stumpff, Friederike (WE 2)

Kongress

100th annual meeting of the German Physiological Society

Frankfurt am Main, 30.09. – 02.10.2021

Quelle

100th annual meeting of the German Physiological Society : book of abstracts : 30.09.– 02.10.2021 Frankfurt am Main — DPG, Deutsche Physiologische Gesellschaft (Hrsg.)

[S.l.], 2021 — S. 414

Sprache

Englisch

Verweise

URL (Volltext): https://www.dpg2021.de/wp-content/uploads/DPG2021_Abstract-Book.pdf

Kontakt

Institut für Veterinär-Physiologie

Oertzenweg 19 b
14163 Berlin
+49 30 838 62600
physiologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Keratinocytes within stratified squamous epithelia such as the skin or the rumen abundantly express TRPV3 channels
with functions that are poorly understood. In the ruminant forestomach, a role in the transport of Ca2+ and NH4+ has
emerged [3,1]. In human skin, TRPV3 participates in the keratinisation process, with gain of function mutations in
humans leading to severe hyperkeratosis [2]. Given the importance of NH4+ for protein metabolism, we wished to find
out if the human homologue hTRPV3 conducts NH4+. Furthermore, while stimulatory effects of L-menthol on TRPV3-
mediated Ca2+ influx are well documented, effects of D-menthol have not been studied.
Accordingly, HEK-293 cells were transiently transfected with a HA-Strep-hTRPV3 construct subcloned into a pIRES2-
AcGFP1 vector, while controls were transfected using the empty vector. Cells were investigated with the whole-cell
configuration of the patch clamp technique. After filling with a Na-Gluconate pipette solution, cells were consecutively
superfused with NaCl or NH4Cl Ringer. Significant rises in inward current and the reversal potential in overexpressing
cells and controls were observed, which suggests that permeability to NH4+ exceeded that to Na+. Simultaneous
stimulation of outward currents carried by Na+ were also observed and may reflect effects of swelling, pH, or activation
of current by a permeant ion. In cells expressing hTRPV3, but not in controls, both inward and outward currents could
be stimulated by either D-menthol or L-menthol. While the effects of a second application of menthol were always
significantly larger than that of the first, no difference between the two enantiomers emerged. The stimulatory effects
of D-menthol on TRPV3 were confirmed via Ca2+ imaging. We conclude that chirality plays no role in the effects of
menthol on TRPV3. Furthermore, like the bovine homologue, the human TRPV3 channel conducts NH4+. In addition
to the well-documented role of the TRPV3 channel in Ca2+ signalling in the human skin, a further function of this non-
selective channel may thus be to supply NH4+ for the synthesis of glutamine and ultimately, involucrin, loricrin, and
filaggrin as building blocks of the corneocyte envelope.