Transmural stretch-dependent regulation of contractile properties in rat heart and its alteration after myocardial infarction.
The "stretch-sensitization" response is essential to the regulation of heart contractility. An increase in diastolic volume improves systolic contraction. The cellular mechanisms of this modulation, the Frank-Starling law, are still uncertain. Moreover, their alterations in heart failure remains controversial. Here, using left ventricular skinned rat myocytes, we show a nonuniform stretch-sensitization of myofilament activation across the ventricular wall. Stretch-dependent Ca2+ sensitization of myofilaments increases from sub-epicardium to sub-endocardium and is correlated with an increase in passive tension. This passive tension-dependent component of myofibrillar activation is not associated with expression of titin isoforms, changes in troponin I level, and phosphorylation status. Instead, we observe that stretch induces phosphorylation of ventricular myosin light chain 2 isoform (VLC2b) in sub-endocardium specifically. Thus, VLC2b phosphorylation could act as a stretch-dependent modulator of activation tuned within normal heart. Moreover, in postmyocardial infarcted rat, the gradient of stretch-dependent Ca2+ sensitization disappears associated with a lack of VLC2b phosphorylation in sub-endocardium. In conclusion, nonuniformity is a major characteristic of the normal adult left ventricle (LV). The heterogeneous myocardial deformation pattern might be caused not only by the morphological heterogeneity of the tissue in the LV wall, but also by the nonuniform contractile properties of the myocytes across the wall. The loss of a contractile transmural gradient after myocardial infarction should contribute to the impaired LV function.
Cazorla
Olivier
O
INSERM U-637, CHU Arnaud de Villeneuve, Montpellier, France.
Szilagyi
Szabolcs
S
Le Guennec
Jean-Yves
JY
Vassort
Guy
G
Lacampagne
Alain
A
D000818:Animals; D024722:Cardiac Myosins / Q000378:metabolism; D003285:Contractile Proteins / Q000378:metabolism*; D006321:Heart; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D024723:Ventricular Myosins / Q000378:metabolism
D003285:Contractile Proteins; D009124:Muscle Proteins; D018994:Myosin Light Chains; D020033:Protein Isoforms; C107184:myosin light chain 2; D024722:Cardiac Myosins; D024723:Ventricular Myosins