Prokineticin 2 potentiates acid-sensing ion channel activity in rat dorsal root ganglion neurons

Background: prokineticin 2 (pk2) is a secreted protein and causes potent hyperalgesia in vivo,and is therefore considered to be a new pronociceptive mediator. however,the molecular targets responsible for the pronociceptive effects of pk2 are still poorly understood. here,we have found that pk2 potentiates the activity of acid-sensing ion channels in the primary sensory neurons.methods: in the present study,experiments were performed on neurons freshly isolated from rat dorsal root ganglion by using whole-cell patch clamp and voltage-clamp recording techniques.results: pk2 dose-dependently enhanced proton-gated currents with an ec50 of 0.22 ± 0.06 nm. pk2 shifted the proton concentration-response curve upwards,with a 1.81 ± 0.11 fold increase of the maximal current response. pk2 enhancing effect on proton-gated currents was completely blocked by pk2 receptor antagonist. the potentiation was also abolished by intracellular dialysis of gf109203x,a protein kinase c inhibitor,or fsc-231,a protein interacting with c-kinase 1 inhibitor. moreover,pk2 enhanced the acid-evoked membrane excitability of rat dorsal root ganglion neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. finally,pk2 exacerbated nociceptive responses to the injection of acetic acid in rats.conclusion: these results suggest that pk2 increases the activity of acid-sensing ion channels via the pk2 receptor and protein kinase c-dependent signal pathways in rat primary sensory neurons. our findings support that pk2 is a proalgesic factor and its signaling likely contributes to acidosis-evoked pain by sensitizing acid-sensing ion channels. © 2012 qiu et al.; licensee biomed central ltd.