Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin
Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin
复制标题
5-羟色胺对海马 CA1 神经元中三个独立 K 电导的差异调节
作者：
A. Colino;J. Halliwell
海马体接收来自中缝核分裂的密集的、含有血清素的神经支配1,2。将血清素应用于海马神经元以模仿内源性递质的作用，通常会产生复杂且可变的反应（例如参见参考文献 3）。使用电压钳方法和对 5-羟色胺受体亚型具有选择性的新配体 4,5，我们已经能够阐明 5-羟色胺对大鼠海马切片 CA1 细胞的作用机制。我们描述了血清素（或 5-HT）对这些细胞中已确定的 K 电导的三种不同作用。首先，它激活不依赖 Ca 的 K 电流，该电流负责神经元超极化并且具有抑制性。其次，它同时抑制缓慢的 Ca 依赖性 K 电导，该电导在很大程度上负责 CA1 神经元 6-8 中细胞放电的调节：这会导致响应去极化输入的神经元放电增加。第三，血清素对固有的电压依赖性 K 电导 Im（参考文献 9）产生更缓慢的发展和持久的抑制，导致神经元去极化和兴奋。超极化反应由 1A 类血清素受体介导，而其他反应则不然。因此，内源性释放的血清素对这些不同电导的调节可以以不同的方式改变哺乳动物大脑中神经元放电的概率或持续时间（或两者），从而产生抑制、兴奋或混合效应。
The hippocampus receives a dense serotonin-containing innervation from the divisions of the raphe nucleus1,2. Serotonin applied to hippocampal neurons to mimic the action of endogenous transmitter often produces complex and variable responses (see for example ref. 3). Using voltage-clamp methods and new ligands that are selective for subtypes of serotonin receptors4,5, we have been able to clarify the mechanism of serotonin action on CA1 cells in rat hippocampal slices. We describe three distinct actions of serotonin (or 5-HT) on identified K-conductances in these cells. First, it activates a Ca-independent K-current which is responsible for neuronal hyperpolarization and is inhibitory. Second, it simultaneously suppresses the slow Ca-dependent K-conductance that is largely responsible for the accommodation of cell firing in CA1 neurons6–8: this produces a paradoxical increase in neuronal dis-charge in response to a depolarizing input. Third, serotonin produces a more slowly developing and long-lasting suppression of an intrinsic voltage-dependent K-conductance, Im (ref. 9), leading to neuronal depolarization and excitation. The hyperpolarizing response is mediated by class 1A serotonin receptors, whereas the other responses are not. Modulation of these different conductances by endogenously released serotonin could therefore change the probability or the duration (or both) of neuronal firing in the mammalian brain in different ways to give inhibitory, excitatory or mixed effects.