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Morfologiia. 2006;129(1):7-17.

[Significance of neuronal, endothelial and inducible NO-synthase isoforms in the cardiac muscle histophysiology].

[Article in Russian]

Abstract

This review summarizes the information on the interrelations between intracellular localization of NO-synthases (NOS) and their regulatory functions within different compartments of a cardiomyocyte in the light of general conception of Barouch et al. (2002) on the intracellular "spatial compartmentalization" of NOS isoforms. Participation of NO in cardiomyocyte function control is based on complex spatial compartmentalization of NOS isoforms: neuronal (NOS1), inducible (NOS2) and endothelial (NOS3), which possess unequal activities resulting in hundredfold differences in the concentrations of gas produced. Regulatory role of constititive Ca-dependent NOS1 and NOS3 is associated with production of low NO concentrations, which cause a decline in cardiomyocyte contractility and a reduction in heart rate. Conversely, Ca-independent inducible NOS2 appears only in the damaged myocardium with a compromised contractile function. NOS2 produces high unregulated NO concentrations, which are connected with the generation of peroxynitrites and NO cytotoxic action. NOS3 is associated with the membranes of cardiomyocyte caveoli and T-tubules, while NOS1 is localized on the sarcoplasmic reticulum membranes. NOS isoform compartmentalization promotes regulation of different circuits in NO-signaling pathways in myocardium, and this principle is a key for understanding of contradictions existing in NO biology in the heart. Changes in NOS subcellular compartmentalization lead to the increased NO synthesis, reduction of the specificity of its effects, disruption of calcium cycle mechanisms, electromechanical uncoupling and myocardial contractility failure. The mechanisms of selective effects of different NO-ergic regulatory pathways on the activity of five major targets in pacemaker and working cardiomyocytes, are discussed.

PMID:
17201313
[PubMed - indexed for MEDLINE]
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