Reduced expression of carbonic anhydrase III in skeletal muscles could be linked to muscle fatigue: A rat muscle fatigue model

Background: Carbonic anhydrase III (CAIII) is expressed abundantly in slow skeletal muscles, adipocytes, and the liver. It plays a critical role in maintaining intracellular pH, antioxidation, and energy metabolism, which are further involved in fatigue. However, its function and mechanism in maintaining the physiological function of muscles or antifatigue are still ambiguous. We hypothesized that changes of CAIII in skeletal muscles might be related to the occurrence of muscle fatigue. Method: After establishing a rat soleus muscle fatigue model, we measured the protein expression of the CAIII in muscles. And the muscle intracellular biochemical indices [malondialdehyde (MDA), adenosine triphosphate (ATP), and lactic acid] were also measured using assay kits. After transfected by CAIII-overexpressing and knockdown lentiviral vectors, the rat soleus muscles were induced to fatigue to investigate the effects and possible molecular mechanisms of CAIII in antifatigue. Results: The expression of CAIII in fatigued soleus muscles was significantly decreased compared with that of the control group (P ​< ​0.001). Moreover, the ATP level in the fatigued muscle also significantly decreased, whereas lactic acid and MDA levels were significantly increased (P ​< ​0.001). After posttransfection for 21 days, CAIII levels in muscles were significantly reduced in the CAIII-interfering lentivirus group, but increased in the CAIII-overexpressed lentivirus group (P ​< ​0.001). In addition, CAIII knockdown muscles showed more reduction of the maximal muscle force and ATP levels ​and more increase of MDA and lactic acid levels during the fatigue test than the control group, (P ​< ​0.05). On the other hand, CAIII-overexpressed muscles showed less reduction of the maximal muscle force and ATP levels and less increase of MDA and lactic acid levels during muscle fatigue than the control group (P ​< ​0.05). Conclusions: Our study showed that soleus muscle fatigue induced by electrical stimulation could result in downregulation of CAIII and ATP levels ​and accumulation of lactic acid and MDA. Further study showed that CAIII knockdown led to more reduction of the maximal muscle force, whereas CAIII overexpression showed less reduction of the maximal muscle force, which suggested that CAIII levels in muscles might be related to the occurrence of muscle fatigue. Translational potential: CAIII plays an important role in muscle fatigue. Up-regulating the expression of CAIII might contribute to dissipating fatigue, which would provide a new method to solve the difficulties in eliminating muscular fatigue.