IL-13 Has a Positive Inotropic Effect Associated with an Increase of Membrane Excitability on Healthy Rat Heart but not in Septic Rat Heart

Abstract

Introduction: Interleukin 13 (IL-13) is a cytokine produced during sepsis. The pro- and/or anti-inflammatory effects of IL-13 still remain not clearly stated, especially at the heart level. In this study, we evidenced the impact of IL-13 on (i) the heart contraction; and on (ii) the voltage-dependent Na+ channels, NaV1.4 and NaV1.5, which are responsible for the membrane excitability, are essential for the excitation/contraction coupling. Methods: Rat hearts were perfused ex vivo with IL-13 at 10ng/ml. The contractile force, heart frequency and coronary flow were recorded. The expression and translocation of NaV1.4 and NaV1.5 were analyzed by western blot after extraction of membrane and cytosol proteins from ventricular cardiomyocytes. Results: Results showed that IL-13 induced an increase of the contractile force (+28.3%), as well as of both maximal speeds of contraction (+35.5%) and relaxation (+38.9%). We also demonstrated that IL-13 was acting via a pathway involving β1-adrenergic - adenylyl cyclase - PKA activation. An increase in sodium current was also shown to be regulated by the same pathway. The hearts perfused with IL-13 showed increased number of NaV1.4 (+37.4%) and NaV1.5 (+52.2%) at the membrane level, and the ratios of membrane/cytosol channels proteins were also increased after IL-13 perfusion for NaV1.4 (+281.4%) and NaV1.5 (+214.4%). Conclusion: This study shows that IL-13 has a positive inotropic effect on perfused heart and that IL-13 can also increase NaV1.4 and NaV1.5 membrane targeting, therefore increasing the membrane excitability of the cardiomyocytes. However, IL-13 was shown to lose its inotropic effects in chronic septic hearts.