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

• Published in: Neurochemical research Vol. 45; no. 12; pp. 2949 - 2958
• Main Authors: Liu, Yamei, Tang, Yunfei, Yan, Jinyu, Du, Dongshu, Yang, Yang, Chen, Fuxue
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-12-2020; Springer Nature B.V
• Subjects: Action potential; Amplitudes; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Brain slice preparation; Cell Biology; Central nervous system; Convulsions & seizures; Dendritic branching; Dendritic structure; Depolarization; EEG; Electroencephalography; Epilepsy; Excitability; Excitatory postsynaptic potentials; Hippocampus; Latency; Membrane potential; Morphology; Neurochemistry; Neurology; Neurons; Neurosciences; Original Paper; Pentylenetetrazole; Postsynaptic density proteins; Potassium; Potassium channels (voltage-gated); Rodents; Seizures; Synapsin I; Epilepsy; Hippocampus; Dendritic arborization; Kv10.2
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-020-03143-7

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.