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Voltage-gated potassium channels and the diversity of electrical signalling

机译:电压门控钾通道和电信号的多样性

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摘要

Since Hodgkin and Huxley discovered the potassium current that underlies the falling phase of action potentials in the squid giant axon, the diversity of voltage-gated potassium (Kv) channels has been manifested in multiple ways. The large and extended potassium channel family is evolutionarily conserved molecularly and functionally. Alternative splicing and RNA editing of Kv channel genes diversify the channel property and expression level. The mix-and-match of subunits in a Kv channel that contains four similar or identical pore-forming subunits and additional auxiliary subunits further diversify Kv channels. Moreover, targeting of different Kv channels to specific subcellular compartments and local translation of Kv channel mRNA in neuronal processes diversify axonal and dendritic action potentials and influence how synaptic plasticity may be modulated. As one indication of the evolutionary conservation of Kv1 channel functions, mutations of the Shaker potassium channel gene in Drosophila and the KCNA1 gene for its mammalian orthologue, Kv1.1, cause hyperexcitability near axon branch points and nerve terminals, thereby leading to uncontrolled movements and recapitulating the episodic ataxia-1 (EA1) symptoms in human patients.
机译:自从Hodgkin和Huxley发现了鱿鱼巨轴突动作电位下降阶段的基础的钾电流以来,电压门控钾(Kv)通道的多样性已经以多种方式表现出来。大的和扩展的钾通道家族在分子和功能上在进化上是保守的。 Kv通道基因的选择性剪接和RNA编辑使通道特性和表达水平多样化。包含四个相似或相同的成孔亚基和其他辅助亚基的Kv通道中的亚基混合匹配进一步使Kv通道多样化。此外,将不同的Kv通道靶向特定的亚细胞区室和在神经元过程中Kv通道mRNA的局部翻译使轴突和树突动作电位多样化,并影响突触可塑性的调节方式。果蝇中摇床钾通道基因的突变和其哺乳动物直系同源物Kv1.1的KCNA1基因的突变是Kv1通道功能进化保守的一个指示,在轴突分支点和神经末梢附近引起过度兴奋,从而导致运动不受控制和概括了人类患者的情节性共济失调1(EA1)症状。

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