title: Calcium uptake by sarcoplasmic reticulum is impaired during the hypodynamic phase of sepsis in the rat heart.
abstract: Alterations of the ATP-dependent Ca2+ uptake in the cardiac sarcoplasmic reticulum (SR) during the 2 hemodynamically distinct phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. The SR vesicles were isolated by sucrose gradient centrifugation. The results show that the rates of ATP-dependent Ca2+ uptake in the cardiac SR were unaffected during the early hyperdynamic phase, whereas they were decreased by 41-46% (P < 0.01) during the late hypodynamic phase of sepsis. Analysis of the kinetics of Ca2+ transport indicates that during the late phase of sepsis, the Vmax values of Ca2+ pump for ATP and Ca2+ were decreased, whereas the affinities of Ca2+ pump for ATP and Ca2+ were unaffected. Magnesium stimulated, whereas vanadate inhibited the ATP-dependent Ca2+ uptake, but the Mg2+-stimulated and the vanadate-inhibited Ca2+ uptake activities were significantly lower during the late sepsis. Phosphorylation of SR by the cAMP-dependent and the calmodulin-dependent protein kinases stimulated the ATP-dependent Ca2+ uptake in the control and the early septic experiments, whereas it failed to stimulate Ca2+ uptake in the late sepsis. The extent of the phosphorylation-stimulated Ca2+ uptake activities was reduced by 65-69% (P < 0.01) during the early sepsis, and they were completely abolished during the late sepsis. These data indicate that the ATP-dependent Ca2+ uptake in cardiac SR was impaired during the late hypodynamic phase of sepsis. The impaired Ca2+ uptake during late sepsis was associated with a defective phosphorylation of SR proteins. Because the ATP-dependent Ca2+ uptake by cardiac SR plays an important role in the regulation of contraction-relaxation coupling, our findings may contribute to the understanding of the pathogenesis of altered cardiac function during the progression of sepsis.
authors.affiliation: Department of Pathophysiology, Beijing Medical University, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Ji
authors.forename: L W
authors.initials: LW
authors.lastname: Dong
authors.forename: M S
authors.initials: MS
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000493:pharmacokinetics*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D014638:Vanadates / Q000494:pharmacology
chemical_list: D011506:Proteins; D014638:Vanadates; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium