Sarcoplasmic reticulum Ca²⁺ pump expression in denervated skeletal muscle

This study was undertaken as one approach to better understand how contractile activity regulates excitation-contraction coupling phenotype in skeletal muscle. The effects of denervation on the expression of the sarcoplasmic reticulum (SR) Ca²⁺-adenosinetriphosphatase (ATPase), a key protein of the contraction-relaxation cycle, was analyzed in fast-twitch (FT) and slow-twitch (ST) skeletal muscle. Muscle mass, mRNA, and protein expression of specific isoforms of the sarco(endo)plasmic reticulum Ca²⁺- ATPase (SERCA) and contractile parameters related to muscle relaxation were measured in rat soleus and extensor digitorum longus (EDL) muscles at 1, 4, 7, 14, and 28 days after sciatic nerve transection. Wet muscle mass decreased to 35% of control by 28 days of denervation in both soleus and EDL muscles (P < 0.05). Northern and Western analyses showed decreases in mRNA and protein expression of the slow Ca²⁺ pump isoform (SERCA2a) in the denervated soleus muscle and in the fast Ca²⁺ pump isoform (SERCA1) in the denervated EDL muscle, particularly at later time points. There was no change in the expression of the alternate isoform in either muscle type. Prolongation of twitch contraction times, slowed rates of tension development, and leftward shifts in frequency-tension curves were consistent with the reduced Ca²⁺ pump density and suggested slowed Ca²⁺ handling in SR of denervated ST and FT muscles. The results are in marked contrast with those previously reported in non-weight-bearing muscle induced by biomechanical unloading.