Mice deficient in TWIK-1 are more susceptible to kainic acid-induced seizures
TWIK-1 belongs to the two-pore domain K<sup>+</sup> (K2P) channel family, which plays an essential role in the background K<sup>+</sup> conductance of cells. Despite the development of exon 2-deleted <i>Twik-1</i> knockout (KO) mice, the physiological role of TWIK-1 has remained largely unknown. Here, we observed that the exon 2-deleted <i>Twik-1</i> KO mice expressed an internally deleted TWIK-1 (TWIK-1 ΔEx2) protein, which unexpectedly acts as a functional K<sup>+</sup> channel. The <i>Twik-1</i> nKO mice in which exon 1 was targeted using the CRISPR-Cas9 technique provides strong evidence that TWIK-1 mediates K<sup>+</sup> currents that are responsible for the background passive conductance in astrocytes. Deficiency of TWIK-1-mediated astrocytic passive conductance increased susceptibility to kainic acid-induced seizures. This study paves the way for functional studies on TWIK-1-mediated astrocytic passive conductance. In addition, the exon 1-targeted <i>Twik-1</i> KO mice would help elucidate the physiological roles of TWIK-1.
Authors
- Eun Mi Hwang (ORCID: https://orcid.org/0000-0002-3130-8572)
- Dawon Kang (ORCID: https://orcid.org/0000-0001-7402-7298)
- Young Hoon Sung (ORCID: https://orcid.org/0000-0002-1508-9883)
- Ae Nim Pae (ORCID: https://orcid.org/0000-0002-3678-8253)
- Jaekwang Lee (ORCID: https://orcid.org/0000-0002-4427-5212)
- Ajung Kim (ORCID: https://orcid.org/0000-0002-1867-6493)
- Esther Yang (ORCID: https://orcid.org/0000-0003-3846-7397)
- Changdev G. Gadhe
- Junyeol Noh
- Yeonju Bae
- Hyun Kim (ORCID: https://orcid.org/0000-0002-7210-5798)
- Eun‐Jin Kim (ORCID: https://orcid.org/0009-0009-9155-9240)
- Jae‐Yong Park (ORCID: https://orcid.org/0000-0001-7698-7890)
- Hyun‐Gug Jung
- Chanseob Shim
Institutions
- Ulsan College (KR)
- Korea University (KR)
- Asan Medical Center (KR)
- University of Ulsan (KR)
- Korea Institute of Brain Science (KR)
- Korean Association Of Science and Technology Studies (KR)
- Korea Institute of Science and Technology (KR)
Publication Details
- Journal
- iScience
- Published
- 2024-12-12
- DOI
- https://doi.org/10.1016/j.isci.2024.111587
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Research Foundation
- Korea Institute of Science and Technology
- National Research Foundation of Korea