Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1 - Aix-Marseille Université Access content directly
Journal Articles Neurobiology of Disease Year : 2022

Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1

Abstract

We recently described new pathogenic variants in VRK1, in patients affected with distal Hereditary Motor Neuropathy associated with upper motor neurons signs. Specifically, we provided evidences that hiPSC-derived Motor Neurons (hiPSC-MN) from these patients display Cajal Bodies (CBs) disassembly and defects in neurite outgrowth and branching. We here focused on the Axonal Initial Segment (AIS) and the related firing properties of hiPSC-MNs from these patients. We found that the patient's Action Potential (AP) was smaller in amplitude, larger in duration, and displayed a more depolarized threshold while the firing patterns were not altered. These alterations were accompanied by a decrease in the AIS length measured in patients' hiPSC-MNs. These data indicate that mutations in VRK1 impact the AP waveform and the AIS organization in MNs and may ultimately lead to the related motor neuron disease.
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hal-03520705 , version 1 (11-01-2022)

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Rémi Bos, Khalil Rihan, Patrice Quintana, Lara El-Bazzal, Nathalie Bernard-Marissal, et al.. Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1. Neurobiology of Disease, 2022, 164, pp.105609. ⟨10.1016/j.nbd.2021.105609⟩. ⟨hal-03520705⟩
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