Deletion of Kv10.2 Causes Abnormal Dendritic Arborization and Epilepsy Susceptibility
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ORIGINAL PAPER
Deletion of Kv10.2 Causes Abnormal Dendritic Arborization and Epilepsy Susceptibility Yamei Liu1 · Yunfei Tang1 · Jinyu Yan1 · Dongshu Du1 · Yang Yang2 · Fuxue Chen1 Received: 17 June 2020 / Revised: 29 September 2020 / Accepted: 1 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The abnormal function of the voltage-gated potassium channel Kv10.2 can induce epilepsy. However, the physiological function of Kv10.2 in the central nervous system remains unclear. In this study, we found that Kv10.2 knockout (KO) increased the complexity of neurons in the CA3 subarea of hippocampus. Kv10.2 KO led to enlarged somata, elongated dendritic length, and increased the number of dendritic tips in cultured rat hippocampus neurons. Kv10.2 KO also increased Synapsin I and PSD95 protein density in cultured rat hippocampal neurons. Whole cell patch-clamp recordings of brain slices in the CA3 subarea of hippocampus revealed that Kv10.2 KO increased the amplitude of spontaneous excitatory postsynaptic currents (sEPSC) and miniature excitatory postsynaptic currents (mEPSC), depolarized the resting membrane potential and increased the action potential firing, reduced the rheobase and increased the input resistance, which results in enhanced neuronal excitability. Furthermore, we made electroencephalogram (EEG) recordings of brain activity in freely moving rats before and after inducing seizures by pentylenetetrazole (PTZ) injection. Kv10.2 KO rats dramatically increased the EEG amplitude during epilepsy. Behavioral observation after seizure induction revealed that Kv10.2 KO rats demonstrated shortened onset latency, prolonged duration, and increased seizure severity when compared with wild type rats. Therefore, this study provides a new link between Kv10.2 and neuronal morphology and higher intrinsic excitability. Keywords Kv10.2 · Epilepsy · Hippocampus · Dendritic arborization
Introduction Epilepsy is one of the most common neurological diseases, and is found in 0.5%–1% of the world’s population. It is characterized by periodic seizures associated with hypersynchronous neuronal discharge [1, 2]. Although epileptic seizures can be generated by almost all regions of the brain, the investigation of the cellular and network mechanisms of epilepsy over the last several decades has focused largely on three structures: the cerebral cortex, the hippocampus (and Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11064-020-03143-7) contains supplementary material, which is available to authorized users. * Fuxue Chen [email protected] 1
School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China
Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA
2
related structures), and the thalamus [3–5]. One common type of epilepsy, temporal lobe epilepsy, often originates in the hippocampus, and the CA3 subfield of hippocampus in particu
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