Ectopic expression of phospholamban in fast-twitch skeletal muscle alters sarcoplasmic reticulum Ca2+ transport and muscle relaxation

被引:25
|
作者
Slack, JP
Grupp, IL
Ferguson, DG
Rosenthal, N
Kranias, EG
机构
[1] UNIV CINCINNATI, COLL MED, DEPT PHARMACOL & CELL BIOPHYS, CINCINNATI, OH 45267 USA
[2] CASE WESTERN RESERVE UNIV, DEPT ANAT, CLEVELAND, OH 44106 USA
[3] MASSACHUSETTS GEN HOSP E, CARDIOVASC RES CTR, CHARLESTOWN, MA 02129 USA
关键词
D O I
10.1074/jbc.272.30.18862
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
There are three isoforms of the sarcoplasmic reticulum Ca2+-ATPase; they are known as SERCA1, SERCA2, and SERCA3. Phospholamban is present in tissues that express the SERCA2 isoform and is an inhibitor of the affinity of SERCA2 for calcium, In vitro reconstitution and cell culture expression studies have shown that phospholamban can also regulate SERCA1, the fast-twitch skeletal muscle isoform, To determine whether regulation 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 phospholamban, Ectopic expression of phospholamban was associated with a decrease in the affinity of SERCA1 for calcium, Assessment of isometric twitch contractions of intact fast-twitch skeletal muscles revealed depressed rates of relaxation in transgenic mice compared with wild-type cohorts, Furthermore, the prolongation of muscle relaxation appeared to correlate with the levels of phospholamban expressed in two transgenic mouse lines, These findings indicate that ectopic expression of phospholamban in fast-twitch skeletal muscle is associated with inhibition of SERCA1 activity and decreased relaxation rates of this muscle.
引用
收藏
页码:18862 / 18868
页数:7
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