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首页> 外文期刊>Neuron >Kir4.1-Dependent Astrocyte-Fast Motor Neuron Interactions Are Required for Peak Strength
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Kir4.1-Dependent Astrocyte-Fast Motor Neuron Interactions Are Required for Peak Strength

机译:Kir4.1依赖性星形胶质细胞 - 快速运动神经元相互作用是峰强度

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摘要

Diversified neurons are essential for sensorimotor function, but whether astrocytes become specialized to optimize circuit performance remains unclear. Large fast α-motor neurons (FαMNs) of spinal cord innervate fast-twitch muscles that generate peak strength. We report that ventral horn astrocytes express the inward-rectifying K+channel Kir4.1 (a.k.a.Kcnj10) around MNs in a VGLUT1-dependent manner. Loss of astrocyte-encodedKir4.1selectively altered FαMN size and function and led to reduced peak strength. Overexpression of Kir4.1 in astrocytes was sufficient to increase MN size through activation of the PI3K/mTOR/pS6 pathway. Kir4.1 was downregulated cell autonomously in astrocytes derived from amyotrophic lateral sclerosis (ALS) patients with SOD1 mutation. However, astrocyte Kir4.1 was dispensable for FαMN survival even?in the mutant SOD1 background. These findings show that astrocyte Kir4.1 is essential for maintenance of peak strength and suggest that Kir4.1 downregulation might uncouple symptoms of muscle weakness from MN cell death in diseases like ALS.
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