Inflammatory mediators potentiate high affinity GABA(A) currents in rat dorsal root ganglion neurons.
Inflammatory mediators potentiate high affinity GABA(A) currents in rat dorsal root ganglion neurons.
复制标题
DOI：
10.1016/j.neulet.2012.04.068
复制
发表时间：
2012-06-19
影响因子：
2.5
通讯作者：
Gold MS
中科院分区：
文献类型：
--
作者：
Lee KY;Gold MS
在急性组织损伤后，动作电位可以在终止于脊髓背角的传入过程中启动，其向外传播回到外周，该过程被称为背根反射（DRR）。DRR依赖于GABAA受体的激活。流行的假设是，DRR是由于损伤诱导的Na+-K+-Cl−-协同转运蛋白激活后氯平衡电位（ECl）的去极化偏移所致。由于组织损伤后脊髓中也释放炎性介质（IM），如前列腺素E2，以及EC 1已经在初级传入中去极化的证据，另一种假设是IM诱导的GABAA受体介导的电流（IGABA）的增加可能是损伤诱导的DRR增加的基础。为了验证这一假设，我们用标准的全细胞膜片钳技术研究了IM（前列腺素E2（1μM）、缓激肽（10 μM）和组胺（1μM））对分离的大鼠背根神经节（DRG）神经元中IGABA的影响。IM增强中到大直径辣椒素不敏感DRG神经元的亚群中的IGABA。这种效应依赖于GABA的浓度，仅在低浓度（< 10μM）时才表现出来。IM也能增强THIP诱发的电流，IM增强的GABA（1 μM）诱发的紧张性电流对gabazine（20 μM）有抵抗作用。目前的数据是一致的假设，在IGABA的急性增加有助于出现损伤诱导的DRR。
Following acute tissue injury action potentials may be initiated in afferent processes terminating in the dorsal horn of the spinal cord that are propagated back out to the periphery, a process referred to as a dorsal root reflex (DRR). The DRR is dependent on the activation of GABAA receptors. The prevailing hypothesis is that DRR is due to a depolarizing shift in the chloride equilibrium potential (ECl) following an injury-induced activation of the Na+-K+-Cl−-cotransporter. Because inflammatory mediators (IM), such as prostaglandin E2 are also released in the spinal cord following tissue injury, as well as evidence that ECl is already depolarized in primary afferents, an alternative hypothesis is that an IM-induced increase in GABAA receptor mediated current (IGABA) could underlie the injury-induced increase in DRR. To test this hypothesis, we explored the impact of IM (prostaglandin E2 (1μM), bradykinin (10 μM), and histamine (1μM)) on IGABA in dissociated rat dorsal root ganglion (DRG) neurons with standard whole cell patch clamp techniques. IM potentiated IGABA in a subpopulation of medium to large diameter capsaicin insensitive DRG neurons. This effect was dependent on the concentration of GABA, manifest only at low concentrations (< 10μM). THIP evoked current were also potentiated by IM and GABA (1 μM) induced tonic currents enhanced by IM were resistant to gabazine (20 μM). The present data are consistent with the hypothesis that an acute increase in IGABA contributes to the emergence of injury-induced DRR.
登录
查看更多内容
缓激肽在大鼠感觉神经元中诱导的急性伤害性信号是通过抑制 M 型 K 通道和激活 Ca2 激活的 Cl 通道介导的
影响因子：
15.9
作者：
Liu, Boyi;Linley, John E.;Gamper, Nikita
通讯作者：
Gamper, Nikita
影响因子：
2.5
作者：
Rocha-Gonzalez, Hector I.;Mao, Shihong;Alvarez-Leefmans, Francisco J.
通讯作者：
Alvarez-Leefmans, Francisco J.
影响因子：
3.6
作者：
Cervero, F;Laird, JMA;García-Nicas, E
通讯作者：
García-Nicas, E
影响因子：
3.3
作者：
Lee, K. Y.;Charbonnet, M.;Gold, M. S.
通讯作者：
Gold, M. S.
影响因子：
5.5
作者：
ECCLES, JC;WILLIS, WD;SCHMIDT, R
通讯作者：
SCHMIDT, R