Improvement of Ca2+ Transport and Muscle Relaxation in Skeletal Muscle From Sarcolipin Null Mice

Abstract

Sarcolipin (SLN) is an inhibitor of SERCA type pumps by direct binding. To demonstrate whether ablation of SLN in skeletal muscle might impair skeletal muscle function directly, we analyzed skeletal muscle contractility and Ca2+ uptake in SLN null mice (KO). SLN protein expression in wildtype mice (WT) was found to be highest in the quadriceps and gastrocnemius (G) followed by the diaphragm and soleus (Sol), whereas very little SLN expression was seen in the tibialis anterior or extensor digitorum longus (EDL). No SLN protein was detected in muscles from KO. Compared with WT, Ca2+ uptake was increased in the G and Sol of KO muscles, while no significant difference was observed in the EDL. Contractility measurements of WT and KO Sol and EDL muscles were performed. No differences were seen between WT and KO muscles in peak tetanic force; however, peak twitch force was lower in KO by ~28% but only in Sol. Maximum normalized (s‐1) rates of contraction (+dF/dt) and relaxation (−dF/dt) measured during a twitch contraction were significantly higher in Sol of KO compared with WT (+dF/dt, 50.2±5.9 in KO vs 30.9±1.0 in WT; −dF/dt, 7.2±0.5 in KO vs 5.2±0.5 in WT). There were no differences between KO and WT in +dF/dt or −dF/dt in EDL. These results show that SLN regulates muscle contractility in mouse slow twitch fibers by inhibiting SERCA function and reducing Ca2+ uptake.Supported by HSFO (DHM, PHB, AOG), CIHR (DHM, PHB) and NSERC (ART).