Glucagon-like peptide-1 enhances cardiac L-type Ca2+ currents via activation of the cAMP-dependent protein kinase A pathway

Cardiovascular Diabetology

Original Investigation

Daniel C Sigg¹  Deborah A Jaye¹  Yong-Fu Xiao¹  Alena Nikolskaya¹ 

[1] Cardiac Rhythm Disease Management, Medtronic, Inc., 8200 Coral Sea Street NE, 55112, Mounds View, MN, USA;

关键词: Liraglutide;    Exenatide;    Ventricular Myocytes;    Intracellular Dialysis;    Intracellular cAMP Content;   

DOI  :  10.1186/1475-2840-10-6

 received in 2010-12-17, accepted in 2011-01-20,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundGlucagon-like peptide-1 (GLP-1) is a hormone predominately synthesized and secreted by intestinal L-cells. GLP-1 modulates multiple cellular functions and its receptor agonists are now used clinically for diabetic treatment. Interestingly, preclinical and clinical evidence suggests that GLP-1 agonists produce beneficial effects on dysfunctional hearts via acting on myocardial GLP-1 receptors. As the effects of GLP-1 on myocyte electrophysiology are largely unknown, this study was to assess if GLP-1 could affect the cardiac voltage-gated L-type Ca2+ current (ICa).MethodsThe whole-cell patch clamp method was used to record ICa and action potentials in enzymatically isolated cardiomyocytes from adult canine left ventricles.ResultsExtracellular perfusion of GLP-1 (7-36 amide) at 5 nM increased ICa by 23 ± 8% (p < 0.05, n = 7). Simultaneous bath perfusion of 5 nM GLP-1 plus 100 nM Exendin (9-39), a GLP-1 receptor antagonist, was unable to block the GLP-1-induced increase in ICa; however, the increase in ICa was abolished if Exendin (9-39) was pre-applied 5 min prior to GLP-1 administration. Intracellular dialysis with a protein kinase A inhibitor also blocked the GLP-1-enhanced ICa. In addition, GLP-1 at 5 nM prolonged the durations of the action potentials by 128 ± 36 ms (p < 0.01) and 199 ± 76 ms (p < 0.05) at 50% and 90% repolarization (n = 6), respectively.ConclusionsOur data demonstrate that GLP-1 enhances ICa in canine cardiomyocytes. The enhancement of ICa is likely via the cAMP-dependent protein kinase A mechanism and may contribute, at least partially, to the prolongation of the action potential duration.

【 授权许可】

CC BY   
© Xiao et al; licensee BioMed Central Ltd. 2011