Fig. 8

The proposed mechanisms by which TAAR1 regulates Kv1.4 channels in TG neurons. Tyramine acts through Go protein-coupled TAAR1, leading to the release of G_βγ subunits. The G_βγ dimer stimulates the downstream nPKC_θ, which selectively modulates Kv1.4 channel activity, resulting in I_A suppression. The signaling cascade mediated by TAAR1 contributes to TG neuronal hyperexcitability and the nociceptive behaviors of tyramine. Neither PKA nor conventional PKC isoforms are involved in the tyramine-mediated I_A response. Nevertheless, whether nPKC_θ phosphorylates Kv1.4 channels directly or acts via some intermediate signaling molecules needs to be further explored