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

Abstract

Aims: Bradykinin type 2 receptor (B(2)R) 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 B(2)R gene deletion will have an impact on myocardial function.Main methods: Isolated cell shortening, patch-clamp technique, Western blot and confocal microscopy.Key findings: Isolated cell shortening measurements showed significant reduction in B(2)R knockout (B(2)R(-/-)) left ventricular cardiac myocytes' shortening. Whole-cell recordings were used to study the electrophysiological aspects of the left ventricular B(2)R(-/-) cardiomyocytes. Results showed: 1) action potential lengthening; 2) unchanged inwardly rectifying K(+) current; 3) reduced transient outward K(+) (I(to)) and L-type Ca(2+) current densities; 5) changes in kinetic properties related to Ito and I(Ca,L). in addition, transient sarcoplasmic reticulum (SR) Ca(2+) release was found to be smaller in B(2)R(-/-) cardiomyocytes. Importantly, evidence is provided that NO constitutive production is, at least in part, responsible for the reported electrophysiological modifications observed in cardiomyocytes from B(2)R(-/-) mice. Surprisingly, NO is not involved in the SR Ca(2+) release reduction as demonstrated in the present study.Significance: Taken together, our findings indicate that B(2)R plays a fundamental role in the regulation of cardiac function and Ca(2+) homeostasis, probably through a NO dependent pathway. These results may contribute to our understanding of the kinins participation in the control of cardiac function. (C) 2010 Elsevier Inc. All rights reserved.Univ Fed Minas Gerais, Dept Biochem & Immunol, Lab Excitable Membranes & Cardiovasc Biol, Inst Biol Sci, Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, Belo Horizonte, MG, BrazilUniv Fed Vicosa, Dept Educ Fis, Ctr Ciencias Biol & Saude, Vicosa, MG, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilWeb of ScienceConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES