STRETCH-ACTIVATED SIGNALING IS MODULATED BY STRETCH MAGNITUDE AND CONTRACTION

Introduction: Stretch therapy is commonly utilized to prevent shortening maladaptation of skeletal muscle. Stretch in combination with isometric contraction prevents shortening, but the signaling mechanisms are not understood. Methods: Using a soleus tenotomy+stretch rat model, the phosphorylation-activation of mechanosensitive kinases (Akt, p70(S6K), p38 MAPK, and ERK1/2) were measured for various stretch magnitudes, set relative to optimal soleus length (Lo). Results: The kinases were not activated by passive stretch until it exceeded the normal physiological range. Stretch+isometric contraction resulted in relatively strong phosphorylation, even at short lengths. Conclusions: Whereas passive stretch results in kinase phosphorylation only during extreme lengthening, isometric contraction generated pronounced phosphorylation of kinases at Lo and Lo+25%, indicating stimulation of pathways that lead to the preservation or increase of muscle length. Understanding the effects of passive and active stretch with respect to Lo and contraction is essential for predicting therapeutic outcomes and influencing optimal muscle length. Muscle Nerve49: 98-107, 2014