The cAMP transduction cascade mediates the PGE2-induced inhibition of potassium currents in rat sensory neurones
The cAMP transduction cascade mediates the PGE2-induced inhibition of potassium currents in rat sensory neurones
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DOI：
10.1111/j.1469-7793.1999.163aa.x
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发表时间：
1999-04-01
影响因子：
5.5
通讯作者：
Nicol, GD
中科院分区：
文献类型：
--
作者：
Evans, AR;Vasko, MR;Nicol, GD
1.采用全细胞膜片钳技术研究了环腺苷酸（cAMP）转导级联在前列腺素E-2（PGE（2））诱导的离体胚胎大鼠感觉神经元钾电流（I-K）降低中的作用.暴露于100 μ M氯苯基硫代腺苷环3 '，5'-单磷酸（cpt-cAMP）或1 μ M PGE（2）分别导致全细胞I-K缓慢抑制34%和36%（20分钟后测量），而该电流激活的电压依赖性没有变化。这两种药物都没有改变电压依赖性失活曲线的形状，表明I-K的抑制不是由失活特性的改变引起的.为了确定PGE（2）介导的I-K抑制是否依赖于cAMP通路的激活，在蛋白激酶A（PKA）抑制剂PKI存在的情况下，将细胞暴露于这种前列腺素。PGE（2）对I-K的抑制作用可被PKI阻断。在PGE（2）不存在的情况下，PKI对I-K的大小没有显著影响。从使用不同预脉冲电压的实验方案中获得的结果表明，cpt-cAMP和PGE（2）介导的抑制I-K的程度与预脉冲电压无关。对照组和处理组电流的相减结果显示，cpt-cAMP-和PGE（2）-敏感电流几乎没有时间依赖性失活。综上所述，这些结果表明，调制电流可能是延迟整流样I-K。暴露于I-K的抑制剂四乙基铵（TEA）或4-氨基吡啶（4-AP），将由电压阶跃引起的控制电流降低40- 50%至+60 mV。在10 mM TEA存在下，用cpt-cAMP处理不会导致I-K的任何进一步抑制。相比之下，在1 mM 4-AP存在下，cpt-cAMP使I-K降低额外的25-30%。这种效应与预脉冲电压无关.这些结果表明，PGE（2）通过激活PKA抑制感觉神经元的外向I-K，这与PGE（2）介导的感觉神经元敏化部分是由于抑制延迟整流器样I-K的观点一致。
1. The role of the cyclic AMP (cAMP) transduction cascade in mediating the prostaglandin E-2 (PGE(2))-induced decrease in potassium current (I-K) was investigated in isolated embryonic rat sensory neurones using the whole-cell patch-clamp recording technique.2. Exposure to 100 mu M chlorophenylthio-adenosine cyclic 3',5'-monophosphate (cpt-cAMP) or 1 mu M PGE(2) caused a slow suppression of the whole-cell I-K by 34 and 36%, respectively (measured after 20 min), without a shift in the voltage dependence of activation for this current. Neither of these agents altered the shape of the voltage-dependent inactivation curve indicating that the suppression of I-K did not result from alterations in the inactivation properties.3. To determine whether the PGE(2)-mediated suppression of I-K depended on activation of the cAMP pathway cells were exposed to this prostanoid in the presence of the protein kinase A (PKA) inhibitor, PKI. The PGE(2)-induced suppression of I-K was prevented by PKI. In the absence of PGE(2), PKI had no significant effect on the magnitude of I-K.4. Results obtained from protocols using different conditioning prepulse voltages indicated that the extent of cpt-cAMP- and PGE(2)-mediated suppression of I-K was independent of the prepulse voltage. The subtraction of control and treated currents revealed that the cpt-cAMP- and PGE(2)-sensitive currents exhibited little time-dependent inactivation. Taken together, these results suggest that the modulated currents may be delayed rectifier-like I-K.5. Exposure to the inhibitors of I-K, tetraethylammonium (TEA) or 4-aminopyridine (4-AP), reduced the control current elicited by a voltage step to +60 mV by 40-50%. In the presence of 10 mM TEA, treatment with cpt-cAMP did not result in any further inhibition of I-K. In contrast, cpt-cAMP reduced I-K by an additional 25-30% in the presence of 1 mM 4-AP. This effect was independent of the conditioning prepulse voltage.6. These results establish that PGE(2) inhibits an outward I-K in sensory neurones via activation of PKA and are consistent with the idea that the PGE(2)-mediated sensitization of sensory neurones results, in part, from an inhibition of delayed rectifier-like I-K.