Mechanistic basis of differences in Ca2+-handling properties of sarcoplasmic reticulum in right and left ventricles of normal rat myocardium

Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada Submitted 27 December 2005 ; accepted in final form 27 January 2006 This study investigated Ca 2+ -cycling properties of sarcoplasmic reticulum (SR) in right ventricle (RV) and left ventricle (LV) of normal rat myocardium. Intracellular Ca 2+ transients and contractile function were monitored in freshly isolated myocytes from RV and LV. SR in RV displayed nearly fourfold lower rates of ATP-energized Ca 2+ uptake in vitro than SR of LV. The Ca 2+ concentration required for half-maximal activation of Ca 2+ transport was nearly twofold higher in SR of RV. The lower Ca 2+ -sequestering activity of SR in RV was accompanied by a matching decrement in Ca 2+ -induced phosphoenzyme formation during the catalytic cycle of the Ca 2+ -pumping ATPase (SERCA2). Western immunoblot analysis showed that protein levels of Ca 2+ -ATPase and its inhibitor phospholamban (PLN) were only 15% lower in SR of RV than in SR of LV. Coimmunoprecipitation experiments revealed that PLN-bound, functionally inert Ca 2+ -ATPase molecules in SR of RV greatly exceed (>50%) that in SR of LV. Endogenous Ca 2+ /calmodulin-dependent protein kinase-mediated phosphorylation of SR substrates did not abolish the huge disparity in SR Ca 2+ pump function between RV and LV. Intracellular Ca 2+ transients, evoked by electrical field stimulation, were significantly prolonged in RV myocytes compared with LV myocytes, mainly because of slow decay of intracellular Ca 2+ concentration. The slow decay of intracellular Ca 2+ concentration in RV and consequent decrease in the speed of RV relaxation may promote temporal synchrony of the end of diastole in RV and LV. The preponderance of functionally silent SR Ca 2+ pumps in RV reflects a higher diastolic reserve required to protect and maintain RV function in the face of a sudden rise in afterload or resistance in the pulmonary circulation. calcium-adenosinetriphosphatase; phospholamban; phosphoenzyme; calcium transient; diastolic reserve Address for reprint requests and other correspondence: N. Narayanan, Dept. of Physiology and Pharmacology, Medical Sciences Bldg., Univ. of Western Ontario, London, ON, Canada N6A 5C1 (e-mail address: njanoor.narayanan{at}schulich.uwo.ca )