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首页> 外文期刊>Journal of neuroinflammation >Prokineticin 2 potentiates acid-sensing ion channel activity in rat dorsal root ganglion neurons
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Prokineticin 2 potentiates acid-sensing ion channel activity in rat dorsal root ganglion neurons

机译：Prokineticin 2增强大鼠背根神经节神经元的酸感应离子通道活性

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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.
机译：背景Prokineticin 2（PK2）是一种分泌蛋白，可在体内引起强烈的痛觉过敏，因此被认为是一种新的伤害感受介质。然而，对PK2的伤害感受作用的分子靶标仍然知之甚少。在这里，我们发现PK2增强了初级感觉神经元中酸敏感离子通道的活性。方法采用全细胞膜片钳和电压钳记录技术，对大鼠背根神经节新鲜分离出的神经元进行实验。结果PK2剂量依赖性地增强了质子门控电流，EC50为0.22±±0.06 nM。 PK2使质子浓度-响应曲线向上移动，最大电流响应增加1.81？±？0.11倍。 PK2受体拮抗剂完全阻止了PK2对质子门控电流的增强作用。通过蛋白激酶C抑制剂GF109203X或与C激酶1抑制剂相互作用的蛋白质FSC-231的细胞内透析，也消除了这种增强作用。此外，PK2增强了大鼠背根神经节神经元的酸诱发膜兴奋性，并导致去极化幅度和酸刺激引起的尖峰数量显着增加。最后，PK2加剧了大鼠注射乙酸后的伤害感受。结论这些结果表明PK2通过PK2受体和蛋白激酶C依赖性信号通路在大鼠原代感觉神经元中增加了酸敏感离子通道的活性。我们的发现支持PK2是一种镇痛因子，其信号转导可能通过敏化酸敏感的离子通道而导致酸中毒诱发的疼痛。

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