| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Internal Medicine, University of Virginia, Charlottesville, Virginia, United States
2 Cellular and Molecular Physiology, Pennsylvania State University, Hershey, United States; Weis Center for Research, Geisinger Medical Center, Danville, United States
3 Weis Center for Research, Geisinger Medical Center, Danville, United States
4 Cellular and Molecular Physiology, Pennsylvania State University, Hershey, United States; Medicine, Pennsylvania State University, Hershey, United States; Weis Center for Research, Geisinger Medical Center, Danville, United States
* To whom correspondence should be addressed. E-mail: jyc1{at}psu.edu.
Phospholemman (PLM), a 72-amino acid sarcolemmal protein, has been shown to regulate contractility and Ca2+ homeostasis in cardiac myocytes. We characterized excitation-contraction coupling in myocytes isolated from PLM-deficient mice back-bred to a pure congenic C57BL/6 background. Cell length, cell width and whole cell capacitance were not different between wild-type and PLM-null myocytes. Compared to wild-type myocytes, Western blots indicated total absence of PLM but no changes in Na+/Ca2+ exchanger, sarcoplasmic reticulum (SR) Ca2+-ATPase, 
1-subunit of Na+-K+-ATPase and calsequestrin levels in PLM-null myocytes. At 5mM extracellular [Ca2+] concentration ([Ca2+]o), contraction and cytosolic [Ca2+] ([Ca2+]i) transient amplitudes and SR [Ca2+] contents in PLM-null myocytes were significantly (p<0.0004) higher than wild-type myocytes. At 0.6 mM [Ca2+]o, however, contraction and [Ca2+]i transient amplitudes and SR [Ca2+] contents were significantly lower in PLM-null than wild-type myocytes. At 1.8 mM [Ca2+]o, the differences in contraction and [Ca2+]i transient amplitudes were no longer apparent. This pattern of contractile and [Ca2+]i transient abnormalities in PLM-null myocytes mimics that observed in adult rat myocytes overexpressing the cardiac Na+/Ca2+ exchanger. Indeed, we have previosuly reported that Na+/Ca2+ exchange currents were higher in PLM-null myocytes. Activation of protein kinase A resulted in increased inotrophy such that there were no longer any contractility differences between the stimulated wild-type and PLM-null myocytes. Protein kinase C stimulation resulted in decreased contractility in both wild-type and PLM-null myocytes. Resting membrane potential and action potential amplitudes were similar, but action potential duration was much prolonged (p<0.04) in PLM-null myocytes. Whole cell Ca2+ current densities were similar between wild-type and PLM-null myocytes, as were the fast and slow inactivation time constants. We conclude that a major function of PLM is regulation of cardiac contractility and Ca2+ fluxes, likely by modulating Na+/Ca2+ exchange activity.
This article has been cited by other articles:
|
|
 |
|
  J. Wang, T. O. Chan, X.-Q. Zhang, E. Gao, J. Song, W. J. Koch, A. M. Feldman, and J. Y. Cheung Induced overexpression of Na+/Ca2+ exchanger transgene: altered myocyte contractility, [Ca2+]i transients, SR Ca2+ contents, and action potential duration Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H590 - H601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Song, X.-Q. Zhang, J. Wang, E. Cheskis, T. O. Chan, A. M. Feldman, A. L. Tucker, and J. Y. Cheung Regulation of cardiac myocyte contractility by phospholemman: Na+/Ca2+ exchange versus Na+-K+-ATPase Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1615 - H1625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Bell, E. Kennington, W. Fuller, K. Dighe, P. Donoghue, J. E. Clark, L.-G. Jia, A. L. Tucker, J. Randall Moorman, M. S. Marber, et al. Characterization of the phospholemman knockout mouse heart: depressed left ventricular function with increased Na-K-ATPase activity Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H613 - H621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Cheung Regulation of cardiac contractility: high time for FXYD Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H584 - H585. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
