TRANSCRIPTIONAL REGULATION OF PHOSPHOLAMBAN GENE AND TRANSLATIONAL REGULATION OF SERCA2 GENE PRODUCES COORDINATE EXPRESSION OF THESE 2 SARCOPLASMIC-RETICULUM PROTEINS DURING SKELETAL-MUSCLE PHENOTYPE SWITCHING

Chronic 1 Hz stimulation of the canine latissimus dorsi muscle produce d a time-dependent switch from the fast-twitch to the slow-twitch phen otype, This included changes in the proteins of the sarcoplasmic retic ulum, After 3 days of muscle stimulation, there was down-regulation of fast-twitch Ca-ATPase (SERCA1a) mRNA and induction of slow-twitch Ca- ATPase (SERCA2a) mRNA; most changes in both mRNAs were nearly complete after 14 days of stimulation, Although the induction of phospholamban mRNA began after 3 days of muscle stimulation, its up-regulation was not completed until the muscle had been stimulated for 42 days, The ti me course of expression of SERCA2a protein was very different from tha t of SERCA2a mRNA, suggesting that SERCA2 gene expression is regulated at the translational as well as the transcriptional level, The time c ourse of expression of phospholamban protein closely followed that of phospholamban mRNA, suggesting that this gene is under transcriptional control, Thus coordinated expression of SERCA2a and phospholamban pro teins is achieved via translational control of the SERCA2 gene and tra nscriptional control of the phospholamban gene.