title: Genetic modulation of the SERCA activity does not affect the Ca(2+) leak from the cardiac sarcoplasmic reticulum.
abstract: The Ca(2+) content in the sarcoplasmic reticulum (SR) determines the amount of Ca(2+) released, thereby regulating the magnitude of Ca(2+) transient and contraction in cardiac muscle. The Ca(2+) content in the SR is known to be regulated by two factors: the activity of the Ca(2+) pump (SERCA) and Ca(2+) leak through the ryanodine receptor (RyR). However, the direct relationship between the SERCA activity and Ca(2+) leak has not been fully investigated in the heart. In the present study, we evaluated the role of the SERCA activity in Ca(2+) leak from the SR using a novel saponin-skinned method combined with transgenic mouse models in which the SERCA activity was genetically modulated. In the SERCA overexpression mice, the Ca(2+) uptake in the SR was significantly increased and the Ca(2+) transient was markedly increased. However, Ca(2+) leak from the SR did not change significantly. In mice with overexpression of a negative regulator of SERCA, sarcolipin, the Ca(2+) uptake by the SR was significantly decreased and the Ca(2+) transient was markedly decreased. Again, Ca(2+) leak from the SR did not change significantly. In conclusion, the selective modulation of the SERCA activity modulates Ca(2+) uptake, although it does not change Ca(2+) leak from the SR.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morimoto
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: hongo@jikei.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hongo
authors.affiliation: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kusakari
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Komukai
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Center for Translational Medicine, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: O-Uchi
authors.affiliation: Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Asahi
authors.affiliation: Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Kinya
authors.initials: K
authors.lastname: Otsu
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurihara
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006439:Hemodynamics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D011510:Proteolipids / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D009124:Muscle Proteins; D011510:Proteolipids; D019837:Ryanodine Receptor Calcium Release Channel; C077258:sarcolipin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
keywords: Aequorin; Ca(2+) transient; Cardiac muscle; Excitation-contraction coupling; Transgenic mouse