Altered skeletal muscle sarco-endoplasmic reticulum Ca²⁺-ATPase calcium transport efficiency after a thermogenic...

Exposure to predator threat induces a rapid and robust increase in skeletal muscle thermogenesis in rats. The central nervous system relays threat information to skeletal muscle through activation of the sympathetic nervous system, but muscle mechanisms mediating this thermogenesis remain unidentified. Given the relevance of sarcolipin-mediated futile calcium cycling through the sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA) pump to mammalian muscle nonshivering thermogenesis, we hypothesized that this plays a role in contextually induced muscle thermogenesis as well. This was assessed by measuring enzymatic activity of SERCA and sarcoplasmic reticulum Ca²⁺ transport, where the apparent coupling ratio (Ca²⁺ uptake rate divided by ATPase activity rate at a standard Ca²⁺ concentration) was predicted to decrease in association with muscle thermogenesis. Sprague-Dawley rats exposed to predator (ferret) odor (PO) showed a rapid decrease in the apparent coupling ratio in the soleus muscle, indicating SERCA uncoupling compared with control-odor-exposed rats. A rat model of high aerobic fitness and elevated muscle thermogenesis also demonstrated soleus muscle SERCA uncoupling relative to their obesity-prone, low-fitness counterparts. Both the high- and low-aerobic fitness rats showed soleus SERCA uncoupling with exposure to PO. Finally, no increase in sarcolipin expression in soleus muscle was detected with PO exposure. This dataset implicates muscle uncoupling of SERCA Ca²⁺ transport and ATP hydrolysis, likely through altered SERCA or sarcolipin function outside of translational regulation, as one contributor to the muscle thermogenesis provoked by exposure to predator threat. These data support the involvement of SERCA uncoupling in both muscle thermogenic induction and enhanced aerobic capacity.