Investigation of the cardiomyocyte dysfunction in bradykinin type 2 receptor knockout mice

AimsBradykinin type 2 receptor (B2R) is the key component to trigger the intracellular signaling pathway in response to bradykinin under physiological conditions. The present study sought to investigate whether the B2R gene deletion will have an impact on myocardial function.Main methodsIsolated cell shortening, patch-clamp technique, Western blot and confocal microscopy.Key findingsIsolated cell shortening measurements showed significant reduction in B2R knockout (B2R−/−) left ventricular cardiac myocytes’ shortening. Whole-cell recordings were used to study the electrophysiological aspects of the left ventricular B2R−/− cardiomyocytes. Results showed: 1) action potential lengthening; 2) unchanged inwardly rectifying K+ current; 3) reduced transient outward K+ (Ito) and L-type Ca2+ current densities; 5) changes in kinetic properties related to Ito and ICa,L. In addition, transient sarcoplasmic reticulum (SR) Ca2+ release was found to be smaller in B2R−/− cardiomyocytes. Importantly, evidence is provided that NO constitutive production is, at least in part, responsible for the reported electrophysiological modifications observed in cardiomyocytes from B2R−/− mice. Surprisingly, NO is not involved in the SR Ca2+ release reduction as demonstrated in the present study.SignificanceTaken together, our findings indicate that B2R plays a fundamental role in the regulation of cardiac function and Ca2+ homeostasis, probably through a NO dependent pathway. These results may contribute to our understanding of the kinins participation in the control of cardiac function.