Sarcolipin (SLN) inhibits sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) 
pumps. To evaluate the physiological significance of SLN in skeletal muscle, we 
compared muscle contractility and SERCA activity between Sln-null and wild-type 
mice. SLN protein expression in wild-type mice was abundant in soleus and red 
gastrocnemius (RG), low in extensor digitorum longus (EDL), and absent from 
white gastrocnemius (WG). SERCA activity rates were increased in soleus and RG, 
but not in EDL or WG, from Sln-null muscles, compared with wild type. No 
differences were seen between wild-type and Sln-null EDL muscles in 
force-frequency curves or maximum rates of force development (+dF/dt). Maximum 
relaxation rates (-dF/dt) of EDL were higher in Sln-null than wild type across a 
range of submaximal stimulation frequencies, but not during a twitch or peak 
tetanic contraction. For soleus, no differences were seen between wild type and 
Sln-null in peak tetanic force or +dF/dt; however, force-frequency curves showed 
that peak force during a twitch and 10-Hz contraction was lower in Sln-null. 
Changes in the soleus force-frequency curve corresponded with faster rates of 
force relaxation at nearly all stimulation frequencies in Sln-null compared with 
wild type. Repeated tetanic stimulation of soleus caused increased (-dF/dt) in 
wild type, but not in Sln-null. No compensatory responses were detected in 
analysis of other Ca(2+) regulatory proteins using Western blotting and 
immunohistochemistry or myosin heavy chain expression using immunofluorescence. 
These results show that 1) SLN regulates Ca(2+)-ATPase activity thereby 
regulating contractile kinetics in at least some skeletal muscles, 2) the 
functional significance of SLN is graded to the endogenous SLN expression level, 
and 3) SLN inhibitory effects on SERCA function are relieved in response to 
repeated contractions thus enhancing relaxation rates.