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Interactions of Nitric Oxide and Cardiac Ion Channels

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Signal Transduction and the Gasotransmitters

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Summary

Nitric oxide (NO) is a uniquely diffusible and reactive molecular messenger that is found in abundance and plays important regulatory roles in the cardiovascular system. NO modulates a wide variety of ion channels in different systems as diverse as neurons, vascular smooth muscles, carotid bodies, pancreatic cells, and hair cells in the inner ear. Indeed, the modulation of ion channels represents one of the important functional effects of NO. In the cardiovascular system, NO significantly modulates the cardiac ryanodine receptor channel, L-type Ca2+ channel, and Na+ channel. The actions of NO are exceedingly multifaceted. There are at least two distinct downstream signaling actions for NO: an indirect pathway via cyclic guanosine 5′-monophosphate (cGMP) production and a direct pathway via protein thiol nitrosylation (S-nitrosylation). In addition, a low level of cGMP can mediate the inactivation of phosphodiesterase type 3, leading to an increased level of cyclic adenosine monophosphate. For example, Ca2+ channels can be stimulated or inhibited under different conditions by different concentrations of NO via indirect or direct pathways. Furthermore, NO modulations can be biphasic and highly sensitive to experimental conditions, such as redox state of the cells, concentrations of NO, temperature, and oxygen tension. More recently, it has been suggested that spatial confinement of different NO synthase (NOS) isoforms may allow NO signaling to have independent, and even opposite, effects on cardiac function. Therefore, a precise knowledge of various pathways and multiple effectors of different NOS enzymes is critical to the development of diagnostic and therapeutic strategies for heart diseases.

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  1. Zhao Zhang
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  2. Kathryn A. Glatter
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  3. Nipavan Chiamvimonvat
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Editors and Affiliations

  1. Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada

    Rui Wang MD, PhD, FAHA

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Zhang, Z., Glatter, K.A., Chiamvimonvat, N. (2004). Interactions of Nitric Oxide and Cardiac Ion Channels. In: Wang, R. (eds) Signal Transduction and the Gasotransmitters. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-806-9_8

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  • DOI: https://doi.org/10.1007/978-1-59259-806-9_8

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