Mice deficient in TWIK-1 are more susceptible to kainic acid-induced seizures
Ajung Kim,
Yeonju Bae,
Changdev G. Gadhe,
Hyun-Gug Jung,
Esther Yang,
Hyun Kim,
Jaekwang Lee,
Chanseob Shim,
Young Hoon Sung,
Junyeol Noh,
Eun-Jin Kim,
Dawon Kang,
Ae Nim Pae,
Eun Mi Hwang,
Jae-Yong Park
Affiliations
Ajung Kim
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
Yeonju Bae
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea
Changdev G. Gadhe
Convergence Research Center for Diagnosis, Treatment and Care system of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
Hyun-Gug Jung
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
Esther Yang
Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Republic of Korea
Hyun Kim
Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Republic of Korea
Jaekwang Lee
Division of Food Functionality, Korea Food Research Institute, Wanju 55365, Republic of Korea
Chanseob Shim
Elpis-Biotech, Daejeon 35380, Republic of Korea
Young Hoon Sung
Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea; Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
Junyeol Noh
School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea
Eun-Jin Kim
Department of Physiology and Institute of Medical Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea
Dawon Kang
Department of Physiology and Institute of Medical Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea
Ae Nim Pae
Convergence Research Center for Diagnosis, Treatment and Care system of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
Eun Mi Hwang
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Corresponding author
Jae-Yong Park
School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea; Astrion, Seoul 02841, Republic of Korea; Corresponding author
Summary: TWIK-1 belongs to the two-pore domain K+ (K2P) channel family, which plays an essential role in the background K+ conductance of cells. Despite the development of exon 2-deleted Twik-1 knockout (KO) mice, the physiological role of TWIK-1 has remained largely unknown. Here, we observed that the exon 2-deleted Twik-1 KO mice expressed an internally deleted TWIK-1 (TWIK-1 ΔEx2) protein, which unexpectedly acts as a functional K+ channel. The Twik-1 nKO mice in which exon 1 was targeted using the CRISPR-Cas9 technique provides strong evidence that TWIK-1 mediates K+ 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 Twik-1 KO mice would help elucidate the physiological roles of TWIK-1.
