Aim: 

The "stretch-sensitization" response is essential to the regulation of heart contractility. The cellular mechanisms of this modulation, the Frank-Starling law, are still uncertain. Moreover, their alterations in heart failure remain controversial.

Methods: 

We combined in this study micromechanical experiments on skinned rat myocytes and biochemical analysis (Western blot) on skinned strips of myocardium both isolated from the epicardial and endocardial layer.

Results: 

We show a non-uniform stretch-sensitisation of myofilament activation across the ventricular wall. Together with the length-dependent component seen in all cells attributable to interfilament lattice spacing, sub-endocardial cells that are stiffer than sub-epicardial cells also demonstrate a strain-dependent component. This later component of myofilament activation is not correlated with troponin I or titin. Instead, in sub-endocardial tissues specifically, we observe that strain activates phosphorylation of myosin light chain VLC2b. Strain-dependency of contractile properties and phosphorylation of VLC2b are lost in a rat model of post-myocardial infarction.

Conclusion: 

VLC2b phosphorylation appears to be a strain-dependent modulator of activation tuned within normal heart and altered in pathology. A transmural gradient of strain-dependent component of myofilament activation predominant in endocardium allows this tissue to participate equally to epicardium in ventricular contraction despite less constraint. The lost of transmural adaptation after myocardial infarction contributes to the development of cardiac insufficiency.