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Deletion of Kv10.2 Causes Abnormal Dendritic Arborization and Epilepsy Susceptibility

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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.

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Funding

This work was supported by the Shanghai Municipal Science and Technology Commission (Grant No. 16010500600).

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Authors and Affiliations

  1. School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China

    Yamei Liu, Yunfei Tang, Jinyu Yan, Dongshu Du & Fuxue Chen

  2. Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, 47907, USA

    Yang Yang

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Liu, Y., Tang, Y., Yan, J. et al. Deletion of Kv10.2 Causes Abnormal Dendritic Arborization and Epilepsy Susceptibility. Neurochem Res 45, 2949–2958 (2020). https://doi.org/10.1007/s11064-020-03143-7

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