Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes

Martín G Vila Petroff, Suhn Hee Kim, Salvatore Pepe, Chantal Dessy, Eduardo Marbán, Jean Luc Balligand, Steven J. Sollott

Research output: Contribution to journalArticle

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 Ptdlns-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.

Original languageEnglish (US)
Pages (from-to)867-873
Number of pages7
JournalNature Cell Biology
Volume3
Issue number10
DOIs
StatePublished - 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Petroff, M. G. V., Kim, S. H., Pepe, S., Dessy, C., Marbán, E., Balligand, J. L., & Sollott, S. J. (2001). Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes. Nature Cell Biology, 3(10), 867-873. https://doi.org/10.1038/ncb1001-867