Abstract
The IKs channel, a cardiac potassium channel, consists of the alpha subunit KCNQ1 and the beta subunit KCNE1, contributing to the repolarization phase of the cardiac action potential. Mutations in these genes are associated with the development of lethal arrhythmias called congenital long QT syndromes, which are influenced by sympathetic nerve stimulation and sex hormones, through molecular complexes of the KCNQ1 channel. Our proteomic analysis suggests a relationship between the KCNQ1 molecular complex and sepsis-related signaling. However, the mechanism of this relationship remains unclear. To test whether the IKs channel play a role in sepsis˗induced cardiac dysfunction, we used genetically engineered (IKs˗Tg) mice (13˗20 weeks) expressing human IKs channels (tandem protein of KCNE1 and KCNQ1). We employed a sepsis model, the Cecal Slurry (CS) intraperitoneal injection technique. Compared to wild type mice (C57BL6/J), the IKs˗Tg mice showed a lower disease score and reduced hypothermia following CS injection (6 and 24 hours). To investigate the mechanisms, we examined the electrophysiological properties of patch-clamped ventricular myocytes 1 day after CS injection. In wild type mice, we observed prolongation of action potential duration(n = 5) by CS injection, which was not detected in IKs˗Tg mice, suggesting a protective role in CS-induced cardiac dysfunction(n = 5). The relationship between the in vivo and cellular˗level results remains a subject for future investigation.
