Fig. 9
Illustration of proposed mechanisms of adipoR1 signaling on Cav3.2 channels. Adiponectin acts through the G protein-independent adipoR1, leading to the activation of protein kinase CK2α subunits. CK2α stimulates the downstream conventional PKCβ1, which selectively modulates Cav3.2 channel activity, resulting in an IT increase. The signaling cascade mediated by adipoR1 contributes to TG neuronal hyperexcitability and nociceptive behaviors of adiponectin. Importantly, adipoR1 was upregulated in the injured TG, and blockade of Cav3.2 attenuated adipoR1-mediated pain hypersensitivity in CCI-ION-induced neuropathic pain behaviors. Neither PKA, CaMKII nor novel PKC isoforms are involved in the adiponectin-mediated IT response. Nevertheless, whether PKCβ1 directly phosphorylates Cav3.2 channels or acts via some intermediate signaling molecules needs to be further explored