We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca<sup>2+</sup> release in cardiomyocytes.
- Authors
Petroff, Martín G. Vila; Kim, Suhn Hee; Pepe, Salvatore; Dessy, Chantal; Marbán, Eduardo; Balligand, Jean-Luc; Sollott, Steven J.
- Abstract
Stretching of cardiac muscle modulates contraction through the enhancement of the Ca[sup 2+] transient, but how this occurs is still not known. We found that stretching of myocytes modulates the elementary Ca[sup 2+] release process from ryanodine-receptor Ca[sup 2+]-release channels (RyRCs), Ca[sup 2+] sparks and the electrically stimulated Ca[sup 2+] 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 Ca[sup 2+]-spark frequency that is abolished by inhibiting NOS and PI(3)K. Exogenously generated NO reversibly increases Ca[sup 2+]-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.
- Subjects
HEART cells; CALCIUM; NITRIC oxide
- Publication
Nature Cell Biology, 2001, Vol 3, Issue 10, p867
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb1001-867