Regulation Of Cav3.2 T-type Calcium Channels By The Adiponectin Type 1 Receptor In Dorsal Root Ganglion:roles In Inflammatory Pain

Objective:To investigate the effect and mechanism of adiponectin(ADPN)on T-type calcium channel currents in mouse dorsal root ganglion(DRG)neurons.Methods:The expression of ADPN receptors in mouse dorsal root ganglia were measured by western blot analysis and immunofluorescence.The whole cell patch clamp recording was used to investigate the effect of Adiponectin on T-type calcium current and excitability in small DRG neurons.Meanwhile,the pharmacological methods were used to investigate the mechanism of adiponectin on T-type calcium current and membrane excitabilityResults:1)Western blot results revealed that both AdipoRl and AdipoR2 are endogenously expressed in mouse small-diameter DRG neurons.Double staining in mouse intact DRGs indicated that AdipoRl was heavily colocalized with Cav3.2 channels.2)ADPN enhanced T-type calcium channel currents in a dose-dependent manner.APPN at 100nM reversibly enhanced T-type calcium channel currents by 31.74±5.62%,and enhanced Cav3.2 currents by 25.83± 5.24%.Adiponectin had little effect on Cav3.1 and Cav 3.3 currents.3)Pharmacological results showed that ADPN enhanced T-type calcium channel currents via PLC/IP3/CaMKII pathway.4)Adiponectin significantly enhanced the neuronal excitability of small-diameter dorsal root ganglia,which can be blocked by AdipoRl-siRNA and KN-93.5)Behavioral results showed that ADPN induced mechanical pain hyperalgesia,hot pain hyperalgesia and inflammatory pain hyperalgesia in mouse by regulating the T-type calcium channel and neuronal excitability.Conclusion:In small-diameter DRG neurons of mice,ADPN enhanced T-type calcium channel currents and neuronal excitability in a dose-dependent manner via AdipoRl and PLC/IP3/CaMK? pathway,thus participating in pain regulation.