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

Telezhkin, Vsevolod, Straccia, Marco, Yarova, Polina, Pardo, Monica, Yung, Sun, Vinh, Ngoc-Nga, Hancock, Jane M., Barriga, Gerardo Garcia-Diaz, Brown, David A., Rosser, Anne E., Brown, Jonathan T., Canals, Josep M., Randall, Andrew D., Allen, Nicholas D. and Kemp, Paul J. 2018. Kv7 channels are upregulated during striatal neuron development and promote maturation of human iPSC-derived neurons. Pflügers Archiv European Journal of Physiology 470 (9) , pp. 1359-1376. 10.1007/s00424-018-2155-7

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Springer Verlag (Germany)
ISSN: 0031-6768
Date of First Compliant Deposit: 4 June 2018
Date of Acceptance: 15 May 2018
Last Modified: 12 Jun 2019 02:54
URI: http://orca-mwe.cf.ac.uk/id/eprint/111917

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