Mice deficient in TWIK-1 are more susceptible to kainic acid-induced seizures

Abstract

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 D Ex2) 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.