Format

Send to

Choose Destination
Biochim Biophys Acta Mol Cell Res. 2019 Jul;1866(7):1137-1150. doi: 10.1016/j.bbamcr.2019.01.007. Epub 2019 Jan 16.

Behavioral and electrophysiological changes in female mice overexpressing ORAI1 in neurons.

Author information

1
International Institute of Molecular and Cell Biology in Warsaw, 4 Ks. Trojdena Str., Warsaw 02-109, Poland.
2
International Institute of Molecular and Cell Biology in Warsaw, 4 Ks. Trojdena Str., Warsaw 02-109, Poland. Electronic address: lmajewski@iimcb.gov.pl.
3
Laboratory of Animal Models, Neurobiology Centre, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Str., Warsaw 02-093, Poland.
4
Laboratory of Molecular Neurobiology, Neurobiology Centre, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.

Abstract

Orai proteins form highly selective Ca2+ release-activated channels (CRACs). They play a critical role in store-operated Ca2+ entry (SOCE; i.e., the influx of external Ca2+ that is induced by the depletion of endoplasmic reticulum Ca2+ stores). Of the three Orai homologs that are present in mammals (Orai1-3), the physiological function of Orai1 is the best described. CRACs are formed by both homomeric assemblies and heteromultimers of Orais. Orai1 and Orai2 can form heteromeric channels that differ in conductivity during SOCE, depending on their Orai1-to-Orai2 ratio. The present study explored the potential consequences of ORAI1 overexpression in neurons where the dominant isoform is Orai2. We established the Tg(ORAI1)Ibd transgenic mouse line that overexpresses ORAI1 in brain neurons. We observed seizure-like symptoms in aged (≥15-month-old) female mice but not in males of the same age. The application of kainic acid and bicuculline to slices that were isolated from 8-month-old (±1 month) female Tg(ORAI1)Ibd mice revealed a significantly lower frequency of interictal bursts compared with samples that were isolated from wildtype mice. No differences were observed in male mice of a similar age. A battery of behavioral tests showed that context recognition decreased only in female transgenic mice. The phenotype that was observed in female mice suggests that ORAI1 overexpression may affect neuronal activity in a sex-dependent manner. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.

KEYWORDS:

Behavior; Epilepsy; ORAIs; SOCE; STIMs; Seizures

PMID:
30659848
DOI:
10.1016/j.bbamcr.2019.01.007
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center