Invited Symposium: SERCA-Type of Calcium Pumps and Phospholamban



Phospholamban Ablation and Hyperdynamic Cardiac Function

Reinsertion of Phospholamban into the Knockout Mouse Heart

Functional Unit of Phospholamban In Vivo

Summary and Conclusions


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Phospholamban: the Key Regulator of the SR Calcium Pump and Contractility in Cardiac Muscle

Chu, G. (Department of Pharmacology & Cell Biophysics, University of Cincinnati, USA)
Kranias, E.G. (Department of Pharmacology & Cell Biophysics, University of Cincinnati, USA)

Contact Person: Evangelia G. Kranias (kraniaeg@email.uc.edu)


Phospholamban (PLB) is the regulator of the SERCA2 activity in cardiac sarcoplasmic reticulum (SR). Dephosphorylated PLB inhibits the affinity of SERCA2 for Ca2+, whereas phosphorylation removes its inhibition, facilitating Ca2+ transport into the SR lumen and enhancing cardiac function. The physiological importance of PLB was recently elucidated using genetically-altered mouse models. Ablation of PLB was associated with increased SERCA2 Ca2+ affinity, enhanced contractility and attenuated beta-agonist responses. These alterations were not due to compensatory mechanisms in the Ca2+-handling proteins or the beta-receptor signaling pathway. However, there was a down-regulation of the ryanodine receptor in an attempt to maintain Ca2+ homeostasis in the hyperdynamic PLB knockout hearts. The availability of the PLB null background coupled with a strong cardiac-specific alpha-MHC promoter allowed us to further examine the functional unit (pentamer vs. monomer) of PLB in vivo. Re-introduction of wild-type (pentameric) PLB in the knockout heart was capable of reversing its hyperdynamic function. However, monomeric (C41F) PLB was less effective than pentameric PLB in inhibiting contractility, assessed in isolated cardiomyocytes, perfused hearts or intact animals. These findings suggest that PLB is a key regulator of cardiac function and pentameric assembly of PLB may be necessary for its optimal regulatory effects in vivo.

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Presentation Number SAchu0237
Keywords: phospholamban, Ca2+-ATPase, contractility, calcium, transgenics

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Chu, G.; Kranias, E.G.; (1998). Phospholamban: the Key Regulator of the SR Calcium Pump and Contractility in Cardiac Muscle. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/wuytack/chu0237/index.html
© 1998 Author(s) Hold Copyright