Blocking IP3 Receptors with 2-APB Alters Cellular Signaling during 7-Day Soleus Unloading in Rats

Membrane IP3 receptors (IP3Rs) abound in the sarcoplasmicreticulum, nucleus and mitochondria of muscle fibers. We hypothesizedthat IP3R activation during muscle unloading may elicit a weak Ca²⁺ releasesignal, both cytosolic and nucleoplasmic, which promotes (perhapsin cooperation with other signaling cascades) the activation oftranscription factors and thus leads to the expression or repressionof genes associated with muscle phenotypes. Here, we tested thishypothesis by blocking IP3Rs with 2-APB (2-aminoethoxydiphenyl borate,10 mg/kg in 5% DMSO i.p. daily) in a rat 7-day hindlimb suspension modelof soleus muscle unloading. The blocking of IP3Rs prevented a decreasein the cross-sectional area of both slow and fast soleus musclefibers and thus slowed down the development of atrophic processesin this postural muscle during 7-day hindlimb suspension. Such aneffect of blocking IP3Rs during rat soleus muscle unloading maybe due to preventing a decrease in ribosomal biogenesis and an increasein the expression of autophagy markers ULK-1 and IL-6.