| Autor: |
Li-Guo Jia, Donnet, Claudia, Bogaev, Roberta C., Blatt, Rebecca J., McKinney, Cindy E., Day, Kathleen H., Berr, Stuart S., Jones, Larry R., Moorman, J. Randall, Sweadner, Kathleen J., Tucker, Amy L. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Apr2005, Vol. 288 Issue 4, pH1982-H1988, 7p, 3 Charts |
| Abstrakt: |
Phosphnlemman (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+-xchanger modulator, and Na-KATPase-associated subunit. We have generated a phospholemmandeficient 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-KATPase activity was 50% lower in the phospholemman-deficient hearts. Expression (per unit of membrane protein) of total Na-KATPase was only slightly diminished, but expression of the minor αisoform, 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-KATPase 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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