Misonou Hiroaki, Mohapatra Durga P, Trimmer James S
Department of Pharmacology, 3503 GBSF, School of Medicine, University of California, Davis, CA 95616-8635, USA.
Neurotoxicology. 2005 Oct;26(5):743-52. doi: 10.1016/j.neuro.2005.02.003. Epub 2005 Jun 9.
Neurons use a variety of mechanisms to dynamically control their own signaling capabilities. Regulation of voltage-dependent K+ channel localization and function has long been recognized as a major mechanism to achieve dynamic regulation of intrinsic neuronal excitability in a number of mammalian and non-mammalian neurons. Our recent evidence, together with compelling data from other laboratories, suggests that in mammalian neurons the Kv2.1 channel may play an especially prominent role in determining intrinsic neuronal excitability. Kv2.1 is widely expressed in brain and composes the majority of delayed rectifier K+ current in pyramidal neurons in cortex and hippocampus, and is also widely expressed in interneurons. Dynamic modulation of Kv2.1 localization and function by a mechanism involving activity-dependent Kv2.1 dephosphorylation dramatically impacts intrinsic excitability of neurons. Here we review previous studies of Kv2.1 localization and function in neurons, and summarize recent work regarding dynamic regulation of these characteristics. We also discuss possible roles of the Kv2.1 channel in neuronal and network excitability.
神经元利用多种机制来动态控制自身的信号传导能力。长期以来,人们一直认为电压依赖性钾离子通道定位和功能的调节是在许多哺乳动物和非哺乳动物神经元中实现对内在神经元兴奋性进行动态调节的主要机制。我们最近的证据,以及其他实验室的有力数据表明,在哺乳动物神经元中,Kv2.1通道在决定内在神经元兴奋性方面可能发挥特别突出的作用。Kv2.1在大脑中广泛表达,构成了皮层和海马体锥体细胞中延迟整流钾电流的大部分,并且在中间神经元中也广泛表达。通过一种涉及依赖于活动的Kv2.1去磷酸化的机制对Kv2.1定位和功能进行动态调节,会极大地影响神经元的内在兴奋性。在这里,我们回顾了以往关于Kv2.1在神经元中的定位和功能的研究,并总结了关于这些特性动态调节的最新研究成果。我们还讨论了Kv2.1通道在神经元和网络兴奋性中的可能作用。