The cardiac I_Ks channels composed of both alpha subunit KCNQ1 and beta subunit KCNE1 contribute to the repolarization phase of cardiac action potential. Mutations of I_Ks channel genes are associated with the development of lethal arrhythmias due to congenital QT prolongation syndrome. Furthermore, these arrhythmias are affected by various intracellular regulators such as Ca²⁺, CaM, ATP, PKA, and NO via KCNQ1 molecular complex. Our results suggest that membrane proteomics have a relationship between these complexes and sepsis-related signaling. However, this relationship during sepsis has not been elucidated.
Therefore, we test whether I_Ks channels play a role in sepsis-induced cardiac dysfunction by using genetically engineered (I_Ks-Tg) mice (13-20 weeks, genetic background: C57BL/6J) which express human I_Ks channels (tandem protein of KCNE1 and KCNQ1). A sepsis model, the Cecal Slurry (CS) intraperitoneal injection technique, was employed to investigate the effect of cardiac-specific I_Ks channel expression. We showed that the sepsis score of I_Ks-Tg male mice (n = 7) was significantly lower than that in age-matched wild-type male mice (n = 19). To seek the mechanisms, we test the effects of CS on action potential between I_Ks-Tg mice and wild type mice by path-clamp method. Action potential duration (APD) was prolonged in 1-day wild-type male mice after CS injection. However, CS did not change APD in the I_Ks-Tg male mice. These results suggest that the I_Ks channels have a protective role in CS-induced APD prolongation.