Activation of G-protein-coupled receptor 30 increases T-type calcium currents in trigeminal ganglion neurons via the cholera toxin-sensitive protein kinase A pathway

摘要

G protein-coupled receptor 30 (GPR30) is a seven transmembrane domain G protein coupled receptor. In our study, GPR30 expression was found in trigeminal ganglia (TG) in mice, detected by RT-PCR and western blotting. We examined the effects of GPR30 activation on T-type calcium channels using GPR30-specific compound 1 (G-1), a GPR30-selective agonist, in TG neurons and demonstrated that G-1 induced an increase in T-type calcium channel currents (T-currents) in TGs. Intracellular infusion of GDP-beta-S and pre-treatment of the neurons with cholera toxin (CTX) blocked the effects of G-1, suggesting that the G_s-protein was involved. Intracellular application of the protein kinase A (PKA) inhibitor PKI 6-22 or pretreatment of the neurons with H89 abolished G-1-induced enhancement of T-currents in TG neurons. However, incubation with PKC inhibitor elicited no such effects. In conclusion, our study shows that activation of GPR30 by G-1 increases T-currents via the CTX-sensitive and PKA-dependent pathway.