Mechanistic basis of differences in Ca2+ -handling properties of sarcoplasmic reticulum in right and left ventricles of normal rat myocardium.
This study investigated Ca2+ -cycling properties of sarcoplasmic reticulum (SR) in right ventricle (RV) and left ventricle (LV) of normal rat myocardium. Intracellular Ca2+ 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 Ca2+ uptake in vitro than SR of LV. The Ca2+ concentration required for half-maximal activation of Ca2+ transport was nearly twofold higher in SR of RV. The lower Ca2+ -sequestering activity of SR in RV was accompanied by a matching decrement in Ca2+ -induced phosphoenzyme formation during the catalytic cycle of the Ca2+ -pumping ATPase (SERCA2). Western immunoblot analysis showed that protein levels of Ca2+ -ATPase and its inhibitor phospholamban (PLN) were only approximately 15% lower in SR of RV than in SR of LV. Coimmunoprecipitation experiments revealed that PLN-bound, functionally inert Ca2+ -ATPase molecules in SR of RV greatly exceed (> 50%) that in SR of LV. Endogenous Ca2+/calmodulin-dependent protein 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 with LV myocytes, mainly because of slow decay of intracellular Ca2+ concentration. The slow decay of intracellular Ca2+ 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 Ca2+ 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.
Sathish
V
V
Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada N6A 5C1.
Xu
A
A
Karmazyn
M
M
Sims
S M
SM
Narayanan
N
N
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D016276:Ventricular Function; D016277:Ventricular Function, Left / Q000502:physiology*; D016278:Ventricular Function, Right / Q000502:physiology*
D002118:Calcium