Hypertrophy, increased ejection fraction, and reduced Na-K-ATPase activity in phospholemman-deficient mice

被引:72
作者
Jia, LG
Donnet, C
Bogaev, RC
Blatt, RJ
McKinney, CE
Day, KH
Berr, SS
Jones, LR
Moorman, JR
Sweadner, KJ
Tucker, AL
机构
[1] Univ Virginia, Hlth Syst, Div Cardiovasc Med, Charlottesville, VA 22908 USA
[2] Univ Virginia, Hlth Syst, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA
[3] Univ Virginia, Hlth Syst, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA
[4] Univ Virginia, Hlth Syst, Dept Radiol, Charlottesville, VA 22908 USA
[5] Univ Virginia, Hlth Syst, Dept Biomed Engn, Charlottesville, VA 22908 USA
[6] Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA
[7] Harvard Univ, Sch Med, Boston, MA USA
[8] Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA
[9] Penn State Univ, University Pk, PA 16802 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2005年 / 288卷 / 04期
关键词
FXYD protein family; heart; mouse; knockout;
D O I
10.1152/ajpheart.00142.2004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Phospholemman (FXYD1), a 72-amino acid transmembrane protein abundantly expressed in the heart and skeletal muscle, is a major substrate for phosphorylation in the cardiomyocyte sarcolemma. Biochemical, cellular, and electrophysiological studies have suggested a number of possible roles for this protein, including ion channel modulator, taurine-release channel, Na+/Ca2+ exchanger modulator, and Na-K-ATPase-associated subunit. We have generated a phospholemman-deficient mouse. The adult null mice exhibited increased cardiac mass, larger cardiomyocytes, and ejection fractions that were 9% higher by magnetic resonance imaging compared with wild-type animals. Notably, this occurred in the absence of hypertension. Total Na-K-ATPase activity was 50% lower in the phospholemman-deficient hearts. Expression ( per unit of membrane protein) of total Na-K-ATPase was only slightly diminished, but expression of the minor alpha 2-isoform, which has been specifically implicated in the control of contractility, was reduced by 60%. The absence of phospholemman thus results in a complex response, including a surprisingly large reduction in intrinsic Na-K-ATPase activity, changes in Na-K-ATPase isoform expression, increase in ejection fraction, and increase in cardiac mass. We hypothesize that a primary effect of phospholemman is to modulate the Na-K-ATPase and that its reduced activity initiates compensatory responses.
引用
收藏
页码:H1982 / H1988
页数:7
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