Developmental sensitivity of hippocampal interneurons to ethanol: involvement of the hyperpolarization-activated current, Ih.
Developmental sensitivity of hippocampal interneurons to ethanol: involvement of the hyperpolarization-activated current, Ih.
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DOI：
10.1152/jn.90557.2008
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发表时间：
2009
影响因子：
2.5
通讯作者：
Haidun Yan;Qiang Li;Rebekah L. Fleming;R. Madison;W. A. Wilson;H. Swartzwelder
中科院分区：
文献类型：
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作者：
Haidun Yan;Qiang Li;Rebekah L. Fleming;R. Madison;W. A. Wilson;H. Swartzwelder
乙醇（EtOH）对GABA（A）受体介导的神经传递具有强大的作用，我们先前已经表明，乙醇诱导的海马GABA（A）受体介导的突触传递增强是发育调节的。由于突触抑制部分取决于中间神经元的放电特性，我们研究了乙醇影响位于陷窝层和S层边界附近的海马中间神经元自发放电特性和超极化激活阳离子电流（Ih）的机制。青少年和成年大鼠的辐射状核。乙醇不影响电流注射诱导的动作电位不表现出自发放电的中间神经元。然而，在自发放电的神经元中，乙醇以浓度依赖性方式增强自发动作电位（sAP）的频率，与成年大鼠相比，这种效应在青春期大鼠的中间神经元中更为明显。乙醇还调制后超极化（AHP），通过缩短tau蛋白（慢）衰减时间常数，这一效果在青少年大鼠切片中更为明显。乙醇增加Ih振幅，加速Ih激活动力学，并增加两个年龄组动物中间神经元的最大Ih电导。这些影响在青少年的中间神经元中也更明显，并且在多巴胺能和GABA能阻滞剂存在下持续存在。然而，EtOH未能影响sAP烧制在ZD 7288或氯化铯的存在下。这些结果提示Ih在EtOH对中间神经元自发放电的影响中可能具有重要的机制意义。
Ethanol (EtOH) has powerful effects on GABA(A) receptor-mediated neurotransmission, and we have previously shown that EtOH-induced enhancement of GABA(A) receptor-mediated synaptic transmission in the hippocampus is developmentally regulated. Because synaptic inhibition is determined in part by the firing properties of interneurons, we have investigated the mechanisms whereby EtOH influences the spontaneous firing characteristics and hyperpolarization-activated cation current (Ih) of hippocampal interneurons located in the near to the border of stratum lacunosum moleculare and s. radiatum of adolescent and adult rats. EtOH did not affect current injection-induced action potentials of interneurons that do not exhibit spontaneous firing. However, in neurons that fire spontaneously, EtOH enhanced the frequency of spontaneous action potentials (sAPs) in a concentration-dependent manner, an effect that was more pronounced in interneurons from adolescent rats, compared with adult rats. EtOH also modulated the afterhyperpolarization (AHP) that follows sAPs by shortening the tau(slow) decay time constant, and this effect was more pronounced in slices from adolescent rats. EtOH increased Ih amplitudes, accelerated Ih activation kinetics, and increased the maximal Ih conductance in interneurons from animals in both age groups. These effects were also more pronounced in interneurons from adolescents and persisted in the presence of glutamatergic and GABAergic blockers. However, EtOH failed to affect sAP firing in the presence of ZD7288 or cesium chloride. These results suggest that Ih may be of mechanistic significance in the effect of EtOH on interneuron spontaneous firing.