Redox regulation of cardiac muscle calcium signaling.
Signal transduction for cardiac muscle contraction is regulated by the Ca2+-induced Ca2+-release mechanism. Redox reactions by biological oxidants and antioxidants have been shown to alter the kinetics of Ca2+-induced Ca2+ release. We postulate that altered kinetics of Ca2+-induced Ca2+ release may divert the contractile pool of Ca2+ to elicit excitation-transcription coupling. We provide evidence that redox reactions regulate excitation-transcription coupling by showing that membrane depolarization may activate the GATA4 transcription factor only when the cells are pretreated with hydrogen peroxide. Therefore, redox regulation of the ryanodine receptor may serve as a mechanism to determine whether the contractile pool of Ca2+ should signal gene transcription during excitation-contraction coupling.
Institute for Cardiovascular Sciences and Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA. moradm@gunet.georgetown.edu
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Morad
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Suzuki
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050991:GATA4 Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008954:Models, Biological; D009124:Muscle Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D051381:Rats; D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D000975:Antioxidants; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D009124:Muscle Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel; D013449:Sulfonamides; D014157:Transcription Factors; C017967:W 7; D006861:Hydrogen Peroxide; D005978:Glutathione