Prokineticin2Potentiates Acid-sensing Ion Channel Activity In Rat Dorsal Root Ganglion Neurons

Objective: The research objectives is observed the adjust effects of PK2/PKRs inacid-sensitive ion channels,reveal the mechanisms of pain modulation；Investigatethorough the effects of PK2/PKRs in neuropathic pain；Observed PKRs blockers onpathologicalthe impact of the pain.Methods: Experiments were performed on neurons freshly isolated from rat dorsalroot ganglion (DRG) by using whole-cell patch clamp and voltage-clamp recordingtechniques.Results: PK2dose-dependently enhanced proton-gated currents with an EC50of0.22±0.06nM. PK2shifted the proton concentration–response curve upwards, with1.81±0.11time increase of the maximal current response. PK2enhancing effect onproton-gated currents was completely blocked by PKRA, a selective PK2receptorantagonist. The potentiation also abolished by intracellular dialysis of GF109203X, aprotein kinase C inhibitor, or FSC-231, a PICK1(protein interacting with C-kinase1)inhibitor. Moreover, PK2enhanced acid-evoked membrane excitability of rat DRGneurons and caused a significant increase in the amplitude of the depolarization and thenumber of spikes induced by acid stimuli. Finally, PK2exacerbated nociceptiveresponses to injection of acetic acid in rats.Conclusion: These results suggest that PK2increases the activity of ASICs viaPK2receptor and protein kinase C-dependent signal pathways in rat primary sensoryneurons. Our findings support that PK2is a pro-algesic factor and its signaling likelycontributes to acidosis-evoked pain by sensitizing ASICs.