Sarcolipin (SLN) is an inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPases 
(SERCAs) in vitro, but its function in vivo has not been defined. NF-SLN cDNA 
(SLN tagged N-terminally with a FLAG epitope) was introduced into rat soleus 
muscle in one hindlimb by plasmid injection and electrotransfer. Western 
blotting showed expression and co-immunoprecipitation showed physical 
interaction between NF-SLN and SERCA2a. Contractile properties and SERCA2a 
function were assessed and compared with vector-injected contralateral soleus 
muscles. NF-SLN reduced both peak twitch force (P(t)) (123.9 +/- 12.5 versus 
69.8 +/- 8.9 millinewtons) and tetanic force (P(o)) (562.3 +/- 51.0 versus 300.7 
+/- 56.9 millinewtons) and reduced both twitch and tetanic rates of contraction 
(+dF/dt) and relaxation (-dF/dt) significantly. Repetitive stimulation (750-ms 
trains at 50 Hz once every 2 s for 3 min) showed that NF-SLN increased 
susceptibility to fatigue. These changes in contractile function were observed 
in the absence of endogenous phospholamban, and NF-SLN had no effect on either 
SERCA2a or SERCA1a expression levels. NF-SLN also decreased maximal Ca(2+) 
transport activity at pCa 5 by 31% with no significant change in apparent Ca(2+) 
affinity (6.36 +/- 0.07 versus 6.39 +/- 0.08 pCa units). These results show that 
NF-SLN expression impairs muscle contractile function by inhibiting SERCA 
function and diminishing sarcoplasmic reticulum Ca(2+) stores.