ECTOPIC EXPRESSION OF PHOSPHOLAMBAN IN FAST-TWITCH SKELETAL-MUSCLE ALTERS SARCOPLASMIC-RETICULUM CA2-RELAXATION( TRANSPORT AND MUSCLE)

There are three isoforms of the sarcoplasmic reticulum Ca2+-ATPase; th ey are known as SERCA1, SERCA2, and SERCA3. Phospholamban is present i n tissues that express the SERCA2 isoform and is an inhibitor of the a ffinity of SERCA2 for calcium, In vitro reconstitution and cell cultur e expression studies have shown that phospholamban can also regulate S ERCA1, the fast-twitch skeletal muscle isoform, To determine whether r egulation of SERCA1 by phospholamban can be of physiological relevance , we generated transgenic mice that ectopically express phospholamban in fast-twitch skeletal muscle, a tissue normally devoid of phospholam ban, Ectopic expression of phospholamban was associated with a decreas e in the affinity of SERCA1 for calcium, Assessment of isometric twitc h contractions of intact fast-twitch skeletal muscles revealed depress ed rates of relaxation in transgenic mice compared with wild-type coho rts, Furthermore, the prolongation of muscle relaxation appeared to co rrelate with the levels of phospholamban expressed in two transgenic m ouse lines, These findings indicate that ectopic expression of phospho lamban in fast-twitch skeletal muscle is associated with inhibition of SERCA1 activity and decreased relaxation rates of this muscle.