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Am J Physiol Heart Circ Physiol (February 3, 2006). doi:10.1152/ajpheart.01372.2005
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Submitted on December 27, 2005
Accepted on January 27, 2006

Mechanistic basis of differences in calcium handling properties of sarcoplasmic reticulum in the right and left ventricles of normal rat myocardium

Venkatachalem Sathish1, Ande Xu1, Morris Karmazyn1, Stephen M Sims1, and Njanoor Narayanan1*

1 Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada

* To whom correspondence should be addressed. E-mail: njanoor.narayanan{at}schulich.uwo.ca.

This study investigated the Ca2+ cycling properties of sarcoplasmic reticulum (SR) in the right ventricle (RV) and left ventricle (LV) of normal rat myocardium. In addition, intracellular Ca2+ transients and contractile function were monitored in freshly isolated myocytes from RV and LV. Surprisingly, RV-SR displayed ~4-fold lower rates of ATP-energized Ca2+uptake in vitro, compared with LV-SR. The concentration of Ca2+ required for half-maximal activation of Ca2+ transport was ~2-fold higher in RV-SR. The lower Ca2+ sequestering activity of RV-SR was accompanied by a matching decrement in Ca2+-induced phosphoenzyme formation during the catalytic cycle of the Ca2+-pumping ATPase (SERCA2). Western immunoblotting analysis showed protein levels of Ca2+-ATPase and its inhibitor, phospholamban (PLN), to be only ~15% lower in RV-SR, compared with LV-SR. Co-immunoprecipitation experiments revealed that PLN-bound, functionally inert Ca2+-ATPase molecules in RV-SR greatly exceed (>50% difference) that in LV-SR. Endogenous Ca2+/calmodulin-dependent protein kinase (CaM kinase) mediated phosphorylation of SR substrates did not abolish the huge disparity in SR Ca2+-pump function between RV and LV. Intracellular Ca2+ transients, evoked by electrical field stimulation, were significantly prolonged in RV myocytes, compared to LV myocytes, mainly due to slow [Ca2+]i decay. The slow [Ca2+]i decay in RV, and consequent decrease in the speed of RV relaxation, may serve to promote temporal synchrony of the end of diastole in right and left ventricular chambers. The preponderance of functionally silent SR Ca2+-pumps in RV reflects a higher diastolic reserve required to protect and maintain RV function when faced with a sudden rise in afterload or resistance in the pulmonary circulation.




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