The Role of Stretch-Activated Channels in Mediating mTORC1 Signaling in Isolated Rat Soleus Muscle in Response to Mechanical Stimulation after Functional Unloading

Abstract

The aim of the present work was to identify the role of stretch-activated ion channels (SAC) in the transmission of mechanical signals to the key mTORC1/p70S6k anabolic pathways in the soleus muscle in rats after seven days of functional unloading of the hindlimbs. Functional unloading of the hindlimb muscles was by antiorthostatic suspension (hindlimb suspension, HS). The rats were divided into four groups: 1) group C (animal-house control; 2) C + Gd (controls whose muscles were incubated with the SAC inhibitor GdCl3; 3) HS (functional unloading for seven days); and 4) HS + Gd (a group with seven days of antiorthostatic suspension followed by incubation of muscles with GdCl3). After completion of antiorthostatic suspension, isolated soleus muscles were subjected to a series of eccentric contractions (EC). Muscles from intact animals responded to EC with increases in the phosphorylation of key markers of mTORC1 signaling: p70S6k and rpS6. The extent of mechanically induced increases in the levels of phosphorylation of these protein markers were significantly reduced to essentially identical extents in the “pure” suspension (HS) group and the HS group given the SAC blocker (HS + Gd) as compared with the increase in muscles from intact control group. These results lead to the conclusion that decreases in the mechanically dependent responses of the mTORC1 signal pathway in the soleus muscle in rats after seven days of functional unloading may be linked with inactivation of stretch-activated ion channels.