Calcium transport across the membrane of the sarcoplasmic reticulum (SR) plays 
an important role in the regulation of heart muscle contraction and relaxation. 
The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for 
Ca(2+) up-take by this organelle and is inhibited in a reversible manner by 
phospholamban, another SR membrane protein. Thus, alleviation of 
phospholamban-mediated inhibition of SERCA2a is a potential therapeutic option 
for heart failure and cardiomyopathy. We have now applied the systematic 
evolution of ligands by exponential enrichment protocol to a library of 
single-stranded DNA molecules containing a randomized 40-nucleotide sequence to 
isolate aptamers that bind phospholamban. One of the obtained aptamers, 
designated Apt-9, was found to specifically bind to the cytoplasmic region of 
phospholamban in vitro with high affinity (dissociation constant, approximately 
20 nM). Apt-9 increased the Ca(2+)-dependent ATPase activity of cardiac SR 
vesicles but not that of SR vesicles from skeletal muscle in a 
concentration-dependent manner. It also shifted the Ca(2+) 
concentration-response curve for this ATPase activity to the left. These effects 
of Apt-9 were not mimicked by an oligonucleotide with a scrambled version of the 
Apt-9 sequence. Thus, our results indicate that Apt-9 activates SERCA2a by 
alleviating the inhibitory effect of phospholamban on this ATPase, and they 
suggest that phospholamban-specific aptamers warrant further investigation as 
potential therapeutic agents for heart failure and cardiomyopathy.