ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. II. Modulation of neuronal excitability
ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. II. Modulation of neuronal excitability
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DOI：
10.1152/jn.00341.2003
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发表时间：
2003-09-01
影响因子：
2.5
通讯作者：
Gereau, RW
中科院分区：
文献类型：
--
作者：
Hu, HJ;Gereau, RW
属于蛋白激酶A(PKA)、蛋白激酶C(PKC)和细胞外信号相关激酶(ERK)家族的蛋白激酶被认为是在脊髓背角水平调节伤害性感觉的关键分子，但这些蛋白激酶对背角神经元膜特性的影响却知之甚少。PKA、PKC和ERK对小鼠背角浅层神经元的瞬时钾电流(A-型电流或I-A)具有抑制作用(Hu等人)。2003年)。在这里，我们旨在确定这些激酶对这些神经元的动作电位、放电和膜特性的影响，以评估I-A(和其他电导)的调制在这些神经元中的影响。我们发现，激活PKC和PKA对动作电位的放电有显著影响，反映了背角浅层神经元兴奋性的增加。此外，我们发现PKC和ERK信号通路的抑制剂都降低了背角神经元的兴奋性，这表明这些激酶对这些细胞具有紧张性兴奋作用。与我们的发现一致的是，这些激酶抑制A-型电流，我们发现PKA、PKC和ERK作用于缩短由电流注入引起的去极化后的第一峰潜伏期。此外，这些激酶的激活增加了背角神经元的尖峰频率和动作电位幅度。有趣的是，我们发现PKA和PKC激活剂的作用被ERK信号的抑制剂阻断，提示PKA和PKC可能通过激活ERK而发挥作用。
Protein kinases belonging to the protein kinase A (PKA), protein kinase C (PKC), and extracellular signal-related kinase (ERK) families have been identified as key players in modulating nociception at the level of the spinal cord dorsal horn, yet little is known about the effects of these kinases on membrane properties of the dorsal horn neurons. PKA, PKC, and ERK exert inhibitory effects on transient potassium currents (A-type currents or I-A) in mouse superficial dorsal horn neurons ( Hu et al. 2003). Here we aimed to determine the effects of these kinases on action potential firing and membrane properties of these neurons to evaluate the impact of the modulation of I-A ( and other conductances) in these neurons. We found that activating PKC and PKA has dramatic effects on action potential firing, reflecting an increase in the excitability of superficial dorsal horn neurons. In addition, we found that inhibitors of both PKC and ERK signaling decrease the excitability of dorsal horn neurons, suggesting that these kinases exert a tonic excitation of these cells. Consistent with our findings that these kinases inhibit A-type currents, we found that PKA, PKC, and ERK act to shorten the first-spike latency after depolarization induced by current injection. In addition, activation of these kinases increases spike frequency and action potential amplitude of dorsal horn neurons. Interestingly, we found that the effects of PKA and PKC activators are blocked by inhibitors of ERK signaling, suggesting that PKA and PKC may exert their actions by activation of ERKs.