Invited Review ArticleS-Nitrosylation of Cardiac Ion ChannelsGonzalez, Daniel R PhD*; Treuer, Adriana MSc*; Sun, Qi-An PhD†‡§; Stamler, Jonathan S MD†‡§; Hare, Joshua M MD*Author Information From the *Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL; Divisions of †Pulmonary and ‡Cardiovascular Medicine, Department of Medicine; and §Department of Biochemistry, Duke University Medical Center, Durham, NC. Received for publication May 13, 2009; accepted July 13, 2009. Supported by National Institutes of Health grants RO1HL 65455, PO1-HL 75443, RO1-HL059130 and RO1 HL94849. The authors report no conflicts of interest. Reprints: Joshua M. Hare, MD, Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Clinical Research Building-1124, P.O. Box 019132 (C-205), Miami, FL 33101 (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: September 2009 - Volume 54 - Issue 3 - p 188-195 doi: 10.1097/FJC.0b013e3181b72c9f Buy Metrics Abstract Nitric oxide (NO) exerts ubiquitous signaling via posttranslational modification of cysteine residues, a reaction termed S-nitrosylation. Important substrates of S-nitrosylation that influence cardiac function include receptors, enzymes, ion channels, transcription factors, and structural proteins. Cardiac ion channels subserving excitation-contraction coupling are potentially regulated by S-nitrosylation. Specificity is achieved in part by spatial colocalization of ion channels with nitric oxide synthases (NOSs), enzymatic sources of NO in biologic systems, and by coupling of NOS activity to localized calcium/second messenger concentrations. Ion channels regulate cardiac excitability and contractility in millisecond timescales, raising the possibility that NO-related species modulate heart function on a beat-to-beat basis. This review focuses on recent advances in understanding of NO regulation of the cardiac action potential and of the calcium release channel ryanodine receptor, which is crucial for the generation of force. S-Nitrosylation signaling is disrupted in pathological states in which the redox state of the cell is dysregulated, including ischemia, heart failure, and atrial fibrillationS. © 2009 Lippincott Williams & Wilkins, Inc.