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.
Highlights
Kv7 channels [4] are sub-threshold, voltage-gated potassium ion channels that are widely expressed in mammalian central and peripheral neurons [5]
Since one of the most important mechanisms responsible for setting and maintaining of Vm in the neurons is represented by Kv7 channels [3, 4, 18, 24], the expression of the Kv7.2 and Kv7.3 protein subunits was determined using immunocytochemistry in neurons isolated at E13 and cultured for up to 14 dpp
Evidence has been provided for a role of CaV3.1 voltage-gated L-type Ca2+ channels in the differentiation of neural stem/progenitor cells [9] and of Kv3.1 K+ channels in the proliferation and neuronal differentiation of adult neural precursor cells [43]
Summary
Kv7 channels [4] are sub-threshold, voltage-gated potassium ion channels that are widely expressed in mammalian central and peripheral neurons [5]. They were first described in sympathetic neurons [4] and have subsequently been identified in a variety of neurons including medium spiny neurons (MSNs) of the striatum [33], sensory nociceptive structures [6, 27], hippocampal CA1 pyramidal cells [14, 31, 32], as well as in the substantia nigra [34]. Being a critical determinant of neuronal excitability, regulated expression of Kv7 channels during neuronal differentiation and maturation ought logically to be vital for the progressive
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
