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Taurine is a semi-essential sulfonic acid found at high concentrations in plasma and mammalian tissues which regulates osmolarity, ion channel activity and glucose homeostasis. The structural requirements of GABAA-receptors (GABAAR) gated by taurine are not yet known. We determined taurine potency and efficacy relative to GABA at different types of recombinant GABAAR occurring in central histaminergic neurons of the mouse hypothalamic tuberomamillary nucleus (TMN) which controls arousal. At binary α(1/2)β(1/3) receptors taurine was as efficient as GABA, whereas incorporation of the γ(1/2) subunit reduced taurine efficacy to 60-90% of GABA. The mutation γ(2F77I), which abolishes zolpidem potentiation, significantly reduced taurine efficacy at recombinant and native receptors compared to the wild type controls. As taurine was a full- or super- agonist at recombinant αxβ1δ-GABAAR, we generated a chimeric γ(2) subunit carrying the δ subunit motif around F77 (MTVFLH). At α(1/2)β(1)γ2(MTVFLH) receptors taurine became a super-agonist, similar to δ-containing ternary receptors, but remained a partial agonist at β3-containing receptors. In conclusion, using site-directed mutagenesis we found structural determinants of taurine's partial agonism at γ-containing GABAA receptors. Our study sheds new light on the β1 subunit conferring the widest range of taurine-efficacies modifying GABAAR function under (patho)physiological conditions.

[This corrects the article DOI: 10.1371/journal.pone.0061733.].

Transient receptor potential vanilloid-3 (TRPV3) is a thermo-sensitive ion channel expressed in skin keratinocytes and in a variety of neural cells. It is activated by warmth as well as monoterpenoids including camphor, menthol, dihydrocarveol and 1,8-cineol. TRPV3 is described as a putative nociceptor and previous studies revealed sensitization of the channel during repeated short-term stimulation with different agonists. In the present investigation TRPV3 was transiently expressed in either Xenopus oocytes or HEK293 cells. Whole-cell voltage-clamp techniques were used to characterize the behavior of TRPV3 when challenged with different agonists. Similarly, a human keratinocyte-derived cell line (HaCaT cells) was used to monitor the behavior of native TRPV3 when challenged with different agonists. We report here that prolonged exposure (5-15 minutes) of monoterpenoids results in agonist-specific desensitization of TRPV3. Long-term exposure to camphor and 1,8-cineol elicits desensitizing currents in TRPV3 expressing oocytes, whereas the non-terpenoid agonist 2-APB induces sustained currents. Agonist-specific desensitization of endogenous TRPV3 was also found in HaCaT cells, which may be taken as a representative for the native system. Terpenoids have a long history of use in therapeutics, pharmaceuticals and cosmetics but knowledge about underpinning molecular mechanisms is incomplete. Our finding on agonist-induced desensitization of TRPV3 by some monoterpenoids displays a novel mechanism through which TRP channels could be functionally modulated. Therefore, we conclude that desensitization of TRPV3 channels might be the molecular basis of action for some of the medicinal properties of camphor and 1,8-cineol.