title: Overexpression of SERCA2b in the heart leads to an increase in sarcoplasmic reticulum calcium transport function and increased cardiac contractility.
abstract: The sarcoplasmic reticulum calcium ATPase SERCA2b is an alternate isoform encoded by the SERCA2 gene. SERCA2b is expressed ubiquitously and has a higher Ca(2+) affinity compared with SERCA2a. We made transgenic mice that overexpress the rat SERCA2b cDNA in the heart. SERCA2b mRNA level was approximately approximately 20-fold higher than endogenous SERCA2b mRNA in transgenic hearts. SERCA2b protein was increased 8-10-fold in the heart, whereas SERCA2a mRNA/protein level remained unchanged. Confocal microscopy showed that SERCA2b is localized preferentially around the T-tubules of the SR, whereas SERCA2a isoform is distributed both transversely and longitudinally in the SR membrane. Calcium-dependent calcium uptake measurements showed that the maximal velocity of Ca(2+) uptake was not changed, but the apparent pump affinity for Ca(2+) (K(0.5)) was increased in SERCA2b transgenic mice (0.199 +/- 0.011 micrometer) compared with wild-type control mice (0.269 +/- 0.012 micrometer, p < 0.01). Work-performing heart preparations showed that SERCA2b transgenic hearts had a higher rates of contraction and relaxation, shorter time to peak pressure and half-time for relaxation than wild-type hearts. These data show that SERCA2b is associated in a subcompartment within the sarcoplasmic reticulum of cardiac myocytes. Overexpression of SERCA2b leads to an increase in SR calcium transport function and increased cardiac contractility, suggesting that SERCA2b plays a highly specialized role in regulating the beat-to-beat contraction of the heart.
authors.affiliation: Laboratory of Molecular Cardiology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0542, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Greene
authors.forename: M J
authors.initials: MJ
authors.lastname: Lalli
authors.forename: Y
authors.initials: Y
authors.lastname: Ji
authors.forename: G J
authors.initials: GJ
authors.lastname: Babu
authors.forename: I
authors.initials: I
authors.lastname: Grupp
authors.forename: M
authors.initials: M
authors.lastname: Sussman
authors.forename: M
authors.initials: M
authors.lastname: Periasamy
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D014176:Protein Biosynthesis; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000201:enzymology* / Q000648:ultrastructure; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014158:Transcription, Genetic
chemical_list: C506948:Atp2a2 protein, rat; D007527:Isoenzymes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; D000252:Calcium-Transporting ATPases; D002118:Calcium