Department of Biological Sciences, Kent State University, Kent, Ohio.
Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.
Am J Physiol Regul Integr Comp Physiol. 2022 Nov 1;323(5):R628-R637. doi: 10.1152/ajpregu.00173.2022. Epub 2022 Sep 12.
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 Ca-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 Ca transport, where the apparent coupling ratio (Ca uptake rate divided by ATPase activity rate at a standard Ca 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 Ca 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.
暴露于捕食者威胁会导致大鼠骨骼肌产热迅速而强烈地增加。中枢神经系统通过激活交感神经系统将威胁信息传递给骨骼肌，但介导这种产热的肌肉机制仍未确定。鉴于肌浆球蛋白介导的通过肌浆内质网 Ca-ATP 酶（SERCA）泵的无效钙循环与哺乳动物肌肉非颤抖产热的相关性，我们假设它在上下文诱导的肌肉产热中也发挥作用。这是通过测量 SERCA 的酶活性和肌浆网 Ca 转运来评估的，其中预测在标准 Ca 浓度下，Ca 摄取率除以 ATP 酶活性的表观偶联比（apparent coupling ratio）会随着肌肉产热而降低。暴露于捕食者（雪貂）气味（PO）的 Sprague-Dawley 大鼠在比目鱼肌中表现出表观偶联比的快速下降，表明与对照气味暴露的大鼠相比，SERCA 解偶联。一种高有氧适能和升高的肌肉产热的大鼠模型也显示比目鱼肌 SERCA 解偶联，与肥胖倾向、低适能的大鼠相比。高和低有氧适能的大鼠在暴露于 PO 时均表现出比目鱼肌 SERCA 解偶联。最后，在暴露于 PO 时，比目鱼肌中没有检测到肌浆球蛋白表达的增加。该数据集表明，SERCA Ca 转运和 ATP 水解的肌肉解偶联可能是通过改变 SERCA 或肌浆球蛋白的功能（而不是翻译调节），是暴露于捕食者威胁引起的肌肉产热的一个贡献因素。这些数据支持 SERCA 解偶联在肌肉产热诱导和增强有氧能力中的参与。
