Both sarcolipin (SLN) and phospholamban (PLN) lower the apparent affinity of 
either SERCA1a or SERCA2a for Ca(2+). Since SLN and PLN are coexpressed in the 
heart, interactions among these three proteins were investigated. When SERCA1a 
or SERCA2a were coexpressed in HEK-293 cells with both SLN and PLN, 
superinhibition resulted. The ability of SLN to elevate the content of PLN 
monomers accounts, at least in part, for the superinhibitory effects of SLN in 
the presence of PLN. To evaluate the role of SLN in skeletal muscle, SLN cDNA 
was injected directly into rat soleus muscle and force characteristics were 
analyzed. Overexpression of SLN resulted in significant reductions in both 
twitch and tetanic peak force amplitude and maximal rates of contraction and 
relaxation and increased fatigability with repeated electrical stimulation. 
Ca(2+) uptake in muscle homogenates was impaired, suggesting that overexpression 
of SLN may reduce the sarcoplasmic reticulum Ca(2+) store. SLN and PLN appear to 
bind to the same regulatory site in SERCA. However, in a ternary complex, PLN 
occupies the regulatory site and SLN binds to the exposed side of PLN and to 
SERCA.