Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes
Author: ["Martín G. Vila Petroff","Suhn Hee Kim","Salvatore Pepe","Chantal Dessy","Eduardo Marbán","Jean-Luc Balligand","Steven J. Sollott"]
Publication: Nature Cell Biology
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Abstract
Stretching of cardiac muscle modulates contraction through the enhancement of the Ca2+ transient, but how this occurs is still not known. We found that stretching of myocytes modulates the elementary Ca2+ release process from ryanodine-receptor Ca2+-release channels (RyRCs), Ca2+ sparks and the electrically stimulated Ca2+ transient. Stretching induces PtdIns-3-OH kinase (PI(3)K)-dependent phosphorylation of both Akt and the endothelial isoform of nitric oxide synthase (NOS), nitric oxide (NO) production, and a proportionate increase in Ca2+-spark frequency that is abolished by inhibiting NOS and PI(3)K. Exogenously generated NO reversibly increases Ca2+-spark frequency without cell stretching. We propose that myocyte NO produced by activation of the PI(3)K–Akt–endothelial NOS axis acts as a second messenger of stretch by enhancing RyRC activity, contributing to myocardial contractile activation.
Cite this article
Petroff, M., Kim, S., Pepe, S. et al. Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes. Nat Cell Biol 3, 867–873 (2001). https://doi.org/10.1038/ncb1001-867
