Phospholamban overexpression in rabbit ventricular myocytes does not alter sarcoplasmic reticulum Ca transport.

Abstract

Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts. Our understanding of the function of phospholamban stems primarily from studies in genetically altered mouse models. To evaluate the significance of this protein in larger mammalian species, which exhibit Ca cycling properties similar to humans, we overexpressed phospholamban in adult rabbit cardiomyocytes. Adenoviral-mediated gene transfer, at high multiplicities of infection, resulted in an insignificant 1.22-fold overexpression of phospholamban. There were no effects on twitch Ca-transient amplitude or decay under basal or isoproterenol-stimulated conditions. Furthermore, the SR Ca load and Na/Ca exchanger function were not altered. These apparent differences between phospholamban overexpression in rabbit compared with previous findings in the mouse may be due to a significantly higher (1.5-fold) endogenous phospholamban-to-sarco(endo)plasmic reticulum Ca-ATPase (SERCA) 2a ratio and potential functional saturation of SERCA2a by phospholamban in rabbit cardiomyocytes. The findings suggest that important species-dependent differences in phospholamban regulation of SERCA2a occur. In larger mammals, a higher fraction of SERCA2a pumps are regulated by phospholamban, and this may influence therapeutic strategies to enhance cardiac contractility and functional cardiac reserve.

• Authors: Jason R Waggoner, Kenneth S Ginsburg, Bryan Mitton, Kobra Haghighi, Jeffrey Robbins, Donald M Bers, Evangelia G Kranias
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 296 Issue 3 Pg. H698-703 (Mar 2009) ISSN: 0363-6135 [Print] United States
• PMID: 19112098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Agonists
• Calcium-Binding Proteins
• Sodium-Calcium Exchanger
• phospholamban
• Caffeine
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Atp2a2 protein, mouse
• Isoproterenol
• Calcium

Topics

• Adenoviridae (genetics)
• Adrenergic beta-Agonists (pharmacology)
• Animals
• Biological Transport
• Caffeine (pharmacology)
• Calcium (metabolism)
• Calcium Signaling (drug effects)
• Calcium-Binding Proteins (genetics, metabolism)
• Cells, Cultured
• Genetic Vectors
• Heart Ventricles (metabolism)
• Isoproterenol (pharmacology)
• Mice
• Myocardial Contraction (drug effects)
• Myocytes, Cardiac (drug effects, metabolism)
• Phosphorylation
• Rabbits
• Sarcoplasmic Reticulum (metabolism)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)
• Sodium-Calcium Exchanger (metabolism)
• Transduction, Genetic
• Up-Regulation