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

• Main Authors: Qiu Chun-Yu, Liu Yu-Qiang, Qiu Fang, Wu Jiliang, Zhou Qun-Yong, Hu Wang-Ping
• Format: Article
• Language: English
• Published: BMC 2012-05-01
• Series: Journal of Neuroinflammation
• Subjects: Acid-sensing ion channel; Dorsal root ganglion neuron; Neuronal excitability; Pain; Prokineticin 2; Proton-gated current
• Online Access: http://www.jneuroinflammation.com/content/9/1/108

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>