Kaczmarek Leonard K, Zhang Yalan
Departments of Pharmacology and of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut.
Physiol Rev. 2017 Oct 1;97(4):1431-1468. doi: 10.1152/physrev.00002.2017.
The intrinsic electrical characteristics of different types of neurons are shaped by the K channels they express. From among the more than 70 different K channel genes expressed in neurons, Kv3 family voltage-dependent K channels are uniquely associated with the ability of certain neurons to fire action potentials and to release neurotransmitter at high rates of up to 1,000 Hz. In general, the four Kv3 channels Kv3.1-Kv3.4 share the property of activating and deactivating rapidly at potentials more positive than other channels. Each Kv3 channel gene can generate multiple protein isoforms, which contribute to the high-frequency firing of neurons such as auditory brain stem neurons, fast-spiking GABAergic interneurons, and Purkinje cells of the cerebellum, and to regulation of neurotransmitter release at the terminals of many neurons. The different Kv3 channels have unique expression patterns and biophysical properties and are regulated in different ways by protein kinases. In this review, we cover the function, localization, and modulation of Kv3 channels and describe how levels and properties of the channels are altered by changes in ongoing neuronal activity. We also cover how the protein-protein interaction of these channels with other proteins affects neuronal functions, and how mutations or abnormal regulation of Kv3 channels are associated with neurological disorders such as ataxias, epilepsies, schizophrenia, and Alzheimer's disease.
不同类型神经元的内在电特性由它们所表达的钾通道塑造。在神经元中表达的70多种不同钾通道基因中,Kv3家族电压依赖性钾通道与某些神经元以高达1000赫兹的高速率产生动作电位和释放神经递质的能力独特相关。一般来说,四个Kv3通道Kv3.1 - Kv3.4具有在比其他通道更正的电位下快速激活和失活的特性。每个Kv3通道基因可产生多种蛋白质异构体,这有助于听觉脑干神经元、快速放电的GABA能中间神经元和小脑浦肯野细胞等神经元的高频放电,并有助于调节许多神经元终末的神经递质释放。不同的Kv3通道具有独特的表达模式和生物物理特性,并受到蛋白激酶的不同方式调节。在本综述中,我们涵盖了Kv3通道的功能、定位和调节,并描述了持续神经元活动的变化如何改变通道的水平和特性。我们还涵盖了这些通道与其他蛋白质的蛋白质 - 蛋白质相互作用如何影响神经元功能,以及Kv3通道的突变或异常调节如何与共济失调、癫痫、精神分裂症和阿尔茨海默病等神经疾病相关联。