Kcnj16 knockout produces audiogenic seizures in the Dahl salt-sensitive rat. JCI Insight 2021 Jan 11;6(1)
Date
11/25/2020Pubmed ID
33232300Pubmed Central ID
PMC7821607DOI
10.1172/jci.insight.143251Scopus ID
2-s2.0-85099291307 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
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 AAuthors
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of WisconsinOlena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Peter LaViolette PhD Professor in the Radiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Acoustic StimulationAnimals
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