ERK integrates PKA and PKC signaling in superficial dorsal horn neurons.: I.: Modulation of A-type K+ currents
ERK integrates PKA and PKC signaling in superficial dorsal horn neurons.: I.: Modulation of A-type K+ currents
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DOI：
10.1152/jn.00340.2003
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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;Glauner, KS;Gereau, RW
瞬时外向钾电流（也称为A型电流或I-A）是神经元兴奋性的重要决定因素。在脑中，I-A由蛋白激酶C（PKC）、蛋白激酶A（PKA）和细胞外信号相关激酶（ERK）调节，这三种激酶已被证明是伤害感受的关键调节剂。我们想确定这些激酶对浅层背角神经元中I-A的影响。用培养的小鼠脊髓背角浅层神经元进行全细胞记录，发现PKC和PKA均抑制I-A，且PKC对I-A具有紧张性抑制作用。此外，我们提供的证据支持的假设，PKC和PKA不直接调节I-A，而是作为上游激活剂的ERK，调节I-A。这些结果表明，ERK作为信号整合剂在调制I-A在背角神经元和A型钾电流的调制可能是由PKC，PKA，和ERK介导的中枢敏化方面的基础。
The transient outward potassium currents (also known as A-type currents or I-A) are important determinants of neuronal excitability. In the brain, I-A is modulated by protein kinase C (PKC), protein kinase A (PKA), and extracellular signal-related kinase (ERK), three kinases that have been shown to be critical modulators of nociception. We wanted to determine the effects of these kinases on I-A in superficial dorsal horn neurons. Using whole cell recordings from cultured mouse spinal cord superficial dorsal horn neurons, we found that PKC and PKA both inhibit I-A in these cells, and that PKC has a tonic inhibitory action on I-A. Further, we provide evidence supporting the hypothesis that PKC and PKA do not modulate I-A directly, but rather act as upstream activators of ERKs, which modulate I-A. These results suggest that ERKs serve as signal integrators in modulation of I-A in dorsal horn neurons and that modulation of A-type potassium currents may underlie aspects of central sensitization mediated by PKC, PKA, and ERKs.