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Kcnj16 knockout produces audiogenic seizures in the Dahl salt-sensitive rat. JCI Insight 2021 01 11;6(1)

Date

11/25/2020

Pubmed ID

33232300

Pubmed Central ID

PMC7821607

DOI

10.1172/jci.insight.143251

Scopus ID

2-s2.0-85099291307   3 Citations

Abstract

Kir5.1 is an inwardly rectifying potassium (Kir) channel subunit abundantly expressed in the kidney and brain. We previously established the physiologic consequences of a Kcnj16 (gene encoding Kir5.1) knockout in the Dahl salt-sensitive rat (SSKcnj16-/-), which caused electrolyte/pH dysregulation and high-salt diet-induced mortality. Since Kir channel gene mutations may alter neuronal excitability and are linked to human seizure disorders, we hypothesized that SSKcnj16-/- rats would exhibit neurological phenotypes, including increased susceptibility to seizures. SSKcnj16-/- rats exhibited increased light sensitivity (fMRI) and reproducible sound-induced tonic-clonic audiogenic seizures confirmed by electroencephalography. Repeated seizure induction altered behavior, exacerbated hypokalemia, and led to approximately 38% mortality in male SSKcnj16-/- rats. Dietary potassium supplementation did not prevent audiogenic seizures but mitigated hypokalemia and prevented mortality induced by repeated seizures. These results reveal a distinct, nonredundant role for Kir5.1 channels in the brain, introduce a rat model of audiogenic seizures, and suggest that yet-to-be identified mutations in Kcnj16 may cause or contribute to seizure disorders.

Author List

Manis AD, Palygin O, Isaeva E, Levchenko V, LaViolette PS, Pavlov TS, Hodges MR, Staruschenko A

Authors

Matthew R. Hodges PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Peter LaViolette PhD Associate Professor in the Radiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acoustic Stimulation
Animals
Disease Models, Animal
Electroencephalography
Epilepsy, Reflex
Female
Gene Knockout Techniques
Humans
Hypokalemia
Male
Mutation
Potassium Channels, Inwardly Rectifying
Potassium, Dietary
Rats
Rats, Inbred Dahl
Rats, Transgenic
Seizures
Severity of Illness Index