title: Interaction between increased SERCA2a activity and beta -adrenoceptor stimulation in adult rabbit myocytes.
abstract: Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2a overexpression and phospholamban depletion have been shown to have beneficial effects on contractility in heart failure. However, the high sympathetic tone during development of failure may interact with increases in SERCA2a activity in potentially deleterious ways. We used adenoviral vectors to overexpress SERCA2a or partially downregulate phospholamban in adult rabbit ventricular myocytes in culture and studied the responses of these cells to beta-adrenoceptor stimulation. SERCA2a overexpression and phospholamban depletion had quantitatively similar effects on basal contraction amplitude and in accelerating relaxation. Increasing SERCA2a activity by either strategy had little effect on the increase in contraction amplitude or incidence of arrhythmias with increasing isoproterenol. Maximum acceleration of relaxation by beta-adrenoceptor stimulation was similar to that produced by SERCA2a overexpression. Isoproterenol treatment of SERCA2a-overexpressing or phospholamban-deficient myocytes produced a further modest decrease in relaxation time, with similar final values in both groups. We find no evidence for Ca(2+) overload induced by SERCA2a overexpression alone or in combination with catecholamines.
authors.affiliation: National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW3 6LY, United Kingdom.
authors.forename: Babar
authors.initials: B
authors.lastname: Chaudhri
authors.forename: Federica
authors.initials: F
authors.lastname: Del Monte
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Sian E
authors.initials: SE
authors.lastname: Harding
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D007527:Isoenzymes / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014162:Transfection; D000099211:Phospholamban
chemical_list: D000318:Adrenergic beta-Agonists; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D016373:DNA, Antisense; D004791:Enzyme Inhibitors; D049452:Green Fluorescent Proteins; D007527:Isoenzymes; D008164:Luminescent Proteins; D011943:Receptors, Adrenergic, beta; D011993:Recombinant Fusion Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban