Kv7 channels are upregulated during striatal neuron development and promote maturation of human iPSC-derived neurons

Kv7 通道在纹状体神经元发育过程中上调,促进人类 iPSC 衍生神经元的成熟

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作者:Vsevolod Telezhkin, Marco Straccia, Polina Yarova, Monica Pardo, Sun Yung, Ngoc-Nga Vinh, Jane M Hancock, Gerardo Garcia-Diaz Barriga, David A Brown, Anne E Rosser, Jonathan T Brown, Josep M Canals, Andrew D Randall, Nicholas D Allen, Paul J Kemp

Abstract

Kv7 channels determine the resting membrane potential of neurons and regulate their excitability. Even though dysfunction of Kv7 channels has been linked to several debilitating childhood neuronal disorders, the ontogeny of the constituent genes, which encode Kv7 channels (KNCQ), and expression of their subunits have been largely unexplored. Here, we show that developmentally regulated expression of specific KCNQ mRNA and Kv7 channel subunits in mouse and human striatum is crucial to the functional maturation of mouse striatal neurons and human-induced pluripotent stem cell-derived neurons. This demonstrates their pivotal role in normal development and maturation, the knowledge of which can now be harnessed to synchronise and accelerate neuronal differentiation of stem cell-derived neurons, enhancing their utility for disease modelling and drug discovery.

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