Activation Of G-protein-coupled Receptor30Increases T-type Calcium Currents In Trigeminal Ganglion Neurons Via The Cholera Toxin-sensitive Protein Kinase A Pathway

Objective: To investigate the effects and the related mechanisms of GPR30activation on T-type calcium channel currents using GPR30-specific compound1(G-1),a GPR30-selective agonist, in trigeminal ganglion (TG) neurons in mice.Methods: Molecular biology methods (PCR and Western Blotting) were used todetermine whether GPR30is expressed in the trigeminal ganglion neurons in femalemice. The whole cell current-clamp recordings was used to investigate the effect of G-1on T-type calcium channel currents in small TG neurons and pharmacological methodswas used to clarify its signaling pathways.Results: In this study, we found that GPR30was expressed in the trigeminalganglion (TG). G-1increased T-type calcium channel currents in a dose-dependentmanner in mouse TG neurons. G-1at100nM reversibly increased~26.8%of the peakT-type calcium channel currents. The increasing effect was blocked by GDP-β-S, aselective G protein antagonist and cholera toxin (CTX), the GSαantagonist, indicatingthat GSα was involved. H89pretreatment or intracellular application of PKI6-22,blocked the increasing effect of G-1on T-type calcium channel currents，whileinhibition of protein kinase C (PKC) elicited no such effects.Conclusion: GPR30-selective agonist G-1can increase T-type calcium channelcurrents in small and middle trigeminal ganglion neurons in female mice via aCTX-sensitive PKA pathway.