mitoKATP channel activation in the postanoxic developing heart protects E-C coupling via NO-, ROS-, and PKC-dependent pathways
| Autor: | Eric Raddatz, Alexandre Sarre, Pavel Kucera, Norbert Lange |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Potassium Channels
Physiology Myocardium/metabolism Vasodilator Agents Chick Embryo Mitochondrion Glycine/analogs & derivatives/pharmacology Anoxia/metabolism Enzyme Inhibitors Hypoxia Protein Kinase C Decanoic Acids/pharmacology Enzyme Inhibitors/pharmacology ddc:615 Chemistry Protein Kinase C/antagonists & inhibitors/metabolism Atrioventricular Node/physiology Heart Anatomy Free Radical Scavengers Cell biology Hydroxy Acids/pharmacology NG-Nitroarginine Methyl Ester Circulatory system Atrioventricular Node medicine.symptom Cardiology and Cardiovascular Medicine Anti-Arrhythmia Agents medicine.drug Signal Transduction Free Radical Scavengers/pharmacology Developing heart Glycine Myocardial Reperfusion Injury Nitric Oxide Reactive Oxygen Species/metabolism Physiology (medical) medicine Diazoxide Myocardial Reperfusion Injury/metabolism Animals NG-Nitroarginine Methyl Ester/pharmacology Oxidative Stress/drug effects/physiology Vasodilator Agents/pharmacology Sulfhydryl Compounds Sulfhydryl Compounds/pharmacology Protein kinase C Oxygen/pharmacology Signal Transduction/physiology Myocardium Membrane Proteins Hypoxia (medical) Diazoxide/pharmacology Oxygen Oxidative Stress Nitric Oxide/metabolism E c coupling Membrane Proteins/metabolism Mitokatp channel Hydroxy Acids Reactive Oxygen Species Chickens Decanoic Acids Anti-Arrhythmia Agents/pharmacology Heart/embryology |
| Zdroj: | American Journal of Physiology. Heart and Circulatory Physiology, Vol. 288, No 4 (2005) pp. H1611-H1619 |
| ISSN: | 0363-6135 |
| Popis: | Whereas previous studies have shown that opening of the mitochondrial ATP-sensitive K+ (mitoKATP) channel protects the adult heart against ischemia-reperfusion injury, it remains to be established whether this mechanism also operates in the developing heart. Isolated spontaneously beating hearts from 4-day-old chick embryos were subjected to 30 min of anoxia followed by 60 min of reoxygenation. The chrono-, dromo-, and inotropic disturbances, as well as alterations of the electromechanical delay (EMD), reflecting excitation-contraction (E-C) coupling, were investigated. Production of reactive oxygen species (ROS) in the ventricle was determined using the intracellular fluorescent probe 2′,7′-dichlorofluorescin (DCFH). Effects of the specific mitoKATP channel opener diazoxide (Diazo, 50 μM) or the blocker 5-hydroxydecanoate (5-HD, 500 μM), the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 50 μM), the antioxidant N-(2-mercaptopropionyl)glycine (MPG, 1 mM), and the PKC inhibitor chelerythrine (Chel, 5 μM) on oxidative stress and postanoxic functional recovery were determined. Under normoxia, the baseline parameters were not altered by any of these pharmacological agents, alone or in combination. During the first 20 min of postanoxic reoxygenation, Diazo doubled the peak of ROS production and, interestingly, accelerated recovery of ventricular EMD and the PR interval. Diazo-induced ROS production was suppressed by 5-HD, MPG, or l-NAME, but not by Chel. Protection of ventricular EMD by Diazo was abolished by 5-HD, MPG, l-NAME, or Chel, whereas protection of the PR interval was abolished by l-NAME exclusively. Thus pharmacological opening of the mitoKATP channel selectively improves postanoxic recovery of cell-to-cell communication and ventricular E-C coupling. Although the NO-, ROS-, and PKC-dependent pathways also seem to be involved in this cardioprotection, their interrelation in the developing heart can differ markedly from that in the adult myocardium. |
| Databáze: | OpenAIRE |
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