title: Developmental changes of Ca(2+) handling in mouse ventricular cells from early embryo to adulthood.
abstract: Transplant of immature cardiomyocytes is recently attracting a great deal of interest as a new experimental strategy for the treatment of failing hearts. Full understanding of normal cardiomyogenesis is essential to make this regenerative therapy feasible. We analyzed the molecular and functional changes of Ca(2+) handling proteins during development of the mouse heart from early embryo at 9.5 days postcoitum (dpc) through adulthood. From the early to the late (18 dpc) embryonic stage, mRNAs estimated by the real time PCR for ryanodine receptor (type 2, RyR2), sarcoplasmic reticulum (SR) Ca(2+) pump (type 2, SERCA2) and phospholamban (PLB) increased by 3-15 fold in the values normalized to GAPDH mRNA, although Na(+)/Ca(2+) exchanger (type 1, NCX1) mRNA was unchanged. After birth, there was a further increase in the mRNAs for RyR2, SERCA2 and PLB by 18-33 fold, but a 50% decrease in NCX1 mRNA. The protein levels of RyR2, SERCA2, PLB and NCX1, which were normalized to total protein, showed qualitatively parallel developmental changes. L-type Ca(2+) channel currents (I(Ca-L)) were increased during the development (1.3-fold at 18 dpc, 2.2-fold at adult stage, vs. 9.5 dpc). At 9.5 dpc, the Ca(2+) transient was, unlike adulthood, unaffected by the SR blockers, ryanodine (5 microM) and thapsigargin (2 microM), and also by a blocker of the Ca(2+) entry via Na(+)/Ca(2+) exchanger, KB-R 7943 (1 microM). The Ca(2+) transient was abolished after application of nisoldipine (5 microM). These results indicate that activator Ca(2+) for contraction in the early embryonic stage depends almost entirely on I(Ca-L).
authors.affiliation: Department of Circulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Weiran
authors.initials: W
authors.lastname: Liu
authors.forename: Kenji
authors.initials: K
authors.lastname: Yasui
authors.forename: Tobias
authors.initials: T
authors.lastname: Opthof
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ishiki
authors.forename: Jong-Kook
authors.initials: JK
authors.lastname: Lee
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokota
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D015737:Nisoldipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D000099211:Phospholamban
chemical_list: D000889:Anti-Arrhythmia Agents; D002118:Calcium; D002121:Calcium Channel Blockers; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D004791:Enzyme Inhibitors; D015737:Nisoldipine; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D019284:Thapsigargin; D013890:Thiourea; D000099211:Phospholamban; C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; C110374:sodium-calcium exchanger 1; C506947:Atp2a2 protein, mouse