Bergles D E, Doze V A, Madison D V, Smith S J
Department of Molecular and Cellular Physiology, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, California 94305-5426, USA.
J Neurosci. 1996 Jan 15;16(2):572-85. doi: 10.1523/JNEUROSCI.16-02-00572.1996.
Norepinephrine (NE) causes an increase in the frequency of inhibitory postsynaptic potentials in CA1 pyramidal neurons in vitro. The possibility that this increase in tonic inhibition is caused by an excitatory effect on inhibitory interneurons was investigated through whole-cell recordings from pyramidal cells and both whole-cell and cell-attached patch recordings from visualized interneurons in acute slices of rat hippocampus. Adrenergic agonists caused a large increase in the frequency and amplitude of spontaneous IPSCs recorded from pyramidal cells in the presence of ionotropic glutamate receptor blockers, but they had no effect on either the frequency or the amplitude of action potential-independent miniature IPSCs recorded in tetrodotoxin. This effect was mediated primarily by an alpha adrenoceptor, although a slight beta adrenoceptor-dependent increase in IPSCs was also observed. NE caused interneurons located in all strata to depolarize and begin firing action potentials. Many of these cells had axons that ramified throughout the stratum pyramidale, suggesting that they are responsible for the IPSCs observed in pyramidal neurons. This depolarization was also mediated by an alpha adrenoceptor and was blocked by a selective alpha 1- but not a selective alpha 2-adrenoceptor antagonist. However, a slight beta adrenoceptor-dependent depolarization was detected in those interneurons that displayed time-dependent inward rectification. In the presence of a beta antagonist, NE induced an inward current that reversed near the predicted K+ equilibrium potential and was not affected by changes in intracellular Cl- concentration. In the presence of an alpha 1 antagonist, NE induced an inwardly rectifying current at potentials negative to approximately -70 mV that did not reverse (between -130 and -60 mV), characteristics similar to the hyperpolarization-activated current (lh). However, the depolarizing action of NE is attributable primarily to the alpha 1 adrenoceptor-mediated decrease in K+ conductance and not the beta adrenoceptor-dependent increase in lh. These results provide evidence that NE increases action potential-dependent IPSCs in pyramidal neurons by depolarizing surrounding inhibitory interneurons. This potent excitatory action of NE on multiple classes of hippocampal interneurons may contribute to the NE-induced decrease in the spontaneous activity of pyramidal neurons and the antiepileptic effects of NE observed in vivo.
去甲肾上腺素（NE）可使体外培养的CA1锥体神经元的抑制性突触后电位频率增加。通过对锥体细胞进行全细胞记录以及对大鼠海马急性切片中可视化的中间神经元进行全细胞和细胞贴附膜片钳记录，研究了这种紧张性抑制增加是否由对抑制性中间神经元的兴奋作用引起。在离子型谷氨酸受体阻滞剂存在的情况下，肾上腺素能激动剂可使从锥体细胞记录到的自发性抑制性突触后电流（IPSCs）的频率和幅度大幅增加，但对在河豚毒素中记录的与动作电位无关的微小IPSCs的频率或幅度均无影响。这种效应主要由α肾上腺素受体介导，不过也观察到了轻微的β肾上腺素受体依赖性IPSCs增加。NE可使位于所有层的中间神经元去极化并开始产生动作电位。这些细胞中的许多细胞具有在整个锥体层分支的轴突，这表明它们是在锥体神经元中观察到的IPSCs的来源。这种去极化也由α肾上腺素受体介导，并被选择性α1 - 但不是选择性α2 - 肾上腺素受体拮抗剂阻断。然而，在那些表现出时间依赖性内向整流的中间神经元中检测到了轻微的β肾上腺素受体依赖性去极化。在存在β拮抗剂的情况下，NE诱导出一种内向电流，该电流在接近预测的K + 平衡电位处反转，且不受细胞内Cl - 浓度变化的影响。在存在α1拮抗剂的情况下，NE在负于约 - 70 mV的电位处诱导出一种内向整流电流，该电流不反转（在 - 130至 - 60 mV之间），其特征类似于超极化激活电流（lh）。然而，NE的去极化作用主要归因于α1肾上腺素受体介导的K + 电导降低，而非β肾上腺素受体依赖性的lh增加。这些结果提供了证据，表明NE通过使周围的抑制性中间神经元去极化来增加锥体神经元中与动作电位相关的IPSCs。NE对多类海马中间神经元的这种强大兴奋作用可能有助于NE诱导的锥体神经元自发活动减少以及在体内观察到的NE的抗癫痫作用。
