Mitochondrial production of reactive oxygen species contributes to the β‐adrenergic stimulation of mouse cardiomycytes

• DOI: 10.1113/jphysiol.2010.202838
• Publication Date: 2011-03-01T21:38:06Z
• Authors: Daniel C. Andersson; Jérémy Fauconnier; Takashi Yamada; Alain Lacampagne; Shi‐Jin Zhang; Abram Katz; Håkan Westerblad
• Keywords: Membrane Potential, Mitochondrial; 0301 basic medicine; Patch-Clamp Techniques; Isoproterenol; Adrenergic beta-Agonists; In Vitro Techniques; Myocardial Contraction; Antioxidants; Mitochondria, Heart; Acetylcysteine; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Receptors, Adrenergic, beta; Animals; Myocytes, Cardiac; Calcium Signaling; Reactive Oxygen Species

The sympathetic adrenergic system plays a central role in stress signalling and is often associated with increased production of reactive oxygen species (ROS). Furthermore, the intimately involved regulation cardiomyocyte Ca2+ handling contractility. In this study we hypothesize that endogenously produced ROS contribute to inotropic mechanism β-adrenergic stimulation mouse cardiomyocytes. Cytoplasmic transients, cell shortening were measured freshly isolated cardiomyocytes using confocal microscopy fluorescent indicators. As marker oxidative stress, malondialdehyde (MDA) modification proteins was detected Western blotting. Isoproterenol (ISO), agonist, mitochondrial concentration- cAMP–protein kinase A-dependent but Ca2+-independent manner. Hearts perfused ISO showed twofold increase MDA protein adducts relative control. transient amplitude, contraction L-type current densities (measured whole-cell patch-clamp) these increases diminished by application general antioxidant N-acetylcysteine (NAC) or mitochondria-targeted SS31. conclusion, an integral acute response stimulation. On other hand, chronically sustained development heart failure cardiac arrhythmias prolonged may defects.