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 journalArticlepeer-review


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
Issue number10
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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