Effects of Nitrosation on Cardiac Myocyte Shortening

Abstract

In the heart, there are two pathways for nitric oxide (NO) signaling, the classic cGMP-PKG and S-nitrosation of proteins. The nitrosation pathway involves an oxidation of cysteine thiols by nitrosonium NO+, and can therefore be a significant, reversible post-translational modification of proteins. Previous studies using NO donors such as S-nitroso-N-acetylpenicillamine (SNAP) were unable to resolve between to two pathways. We hypothesized that nitrosation is an important post-translational modifier of myocardial contractility. To test this hypothesis, we examined the effects of S-nitroso-L-cysteine (CysNO), a selective nitrosonium donor that is actively transported into the cell, on sarcomere shortening in unloaded mouse cardiac myocytes. Perfusion of cardiac myocytes with CysNO (30 μM) resulted in the reduction of sarcomere length changes by ∼80%. This period of blunted sarcomere length changes was followed by a ∼15 second exponential recovery in sarcomere length. During the recovery phase, the maximal velocities of shortening and re-lengthening were diminished. Our data suggest a possible in vivo role of NO+ in regulating myocardial contractility.