Activity-dependent hyperpolarization of EGABA is absent in cutaneous DRG neurons from inflamed rats.
Activity-dependent hyperpolarization of EGABA is absent in cutaneous DRG neurons from inflamed rats.
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DOI：
10.1016/j.neuroscience.2013.10.004
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发表时间：
2014-01-03
期刊：
影响因子：
3.3
通讯作者：
Gold MS
中科院分区：
文献类型：
--
作者：
Zhu Y;Zhang XL;Gold MS
在初级传入神经元中GABAA信号从抑制到兴奋的转变似乎有助于炎症诱导的向中枢神经系统（CNS）的传入输入的增加。GABA平衡电位（EGABA）的活性依赖性去极化已在CNS神经元中被描述，其驱动GABAA信号从抑制到兴奋的转变。本研究的目的是确定这种活动依赖性的去极化的EGABA是否发生在初级传入和是否放大持续炎症的去极化。急性分离的逆行标记的皮肤DRG神经元从幼稚和发炎的大鼠进行了研究短杆菌肽穿孔贴片记录。而不是去极化，200个动作电位在2 Hz下传递导致了~10 mV的超极化的EGABA在皮肤神经元从幼稚大鼠。在发炎大鼠的神经元中没有观察到这种超极化。10 µM布美他尼未阻断EGABA的变化。此外，由于GABA的活性依赖性超极化在电解液中不存在HCO 3 −的情况下完全表现出来，因此这种转变不依赖于HCO 3 −-Cl−交换剂活性的变化，尽管有证据表明DRG神经元中的HCO 3 −-Cl−交换剂可能有助于在HCO 3 −存在下建立GABA。虽然GABA的活性依赖性超极化的机制尚未确定，因为这种机制似乎作为一种反馈抑制的形式，促进GABA介导的传入活动的抑制，它可能作为一个新的目标，用于治疗炎症性疼痛。
A shift in GABAA signaling from inhibition to excitation in primary afferent neurons appears to contribute to the inflammation-induced increase in afferent input to the central nervous system (CNS). An activity-dependent depolarization of the GABA equilibrium potential (EGABA) has been described in CNS neurons which drives a shift in GABAA signaling from inhibition to excitation. The purpose of the present study was to determine if such an activity-dependent depolarization of EGABA occurs in primary afferents and whether the depolarization is amplified with persistent inflammation. Acutely dissociated retrogradely labeled cutaneous DRG neurons from naïve and inflamed rats were studied with gramicidin perforated patch recording. Rather than a depolarization, 200 action potentials delivered at 2 Hz resulted in a ~10 mV hyperpolarization of EGABA in cutaneous neurons from naïve rats. No such hyperpolarization was observed in neurons from inflamed rats. The shift in EGABA was not blocked by 10 µM bumetanide. Furthermore, because activity-dependent hyperpolarization of EGABA was fully manifest in the absence of HCO3− in the bath solution, this shift was not dependent on a change in HCO3−-Cl− exchanger activity, despite evidence of HCO3−-Cl− exchangers in DRG neurons that may contribute to the establishment of EGABA in the presence of HCO3−. While the mechanism underlying the activity-dependent hyperpolarization of EGABA has yet to be identified, because this mechanism appears to function as a form of feedback inhibition, facilitating GABA mediated inhibition of afferent activity, it may serve as a novel target for the treatment of inflammatory pain.
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持续的炎症会增加GABA诱导的大鼠皮肤背根神经神经元的去极化。
影响因子：
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作者：
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