Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes

Mathis K. Stokke, Karina Hougen, Ivar Sjaastad, William E. Louch, Sarah J. Briston, Ulla H. Enger, Kristin B. Andersson, Geir Christensen, David A. Eisner, Ole M. Sejersted, Andrew W. Trafford

    Research output: Contribution to journalArticlepeer-review


    Aims: To describe the overall role of reduced sarcoplasmic reticulum Ca2+ ATPase (SERCA2) for Ca2+ wave development. Methods and results: SERCA2 knockout [Serca2flox/flox Tg(αMHC- MerCreMer); KO] mice allowing inducible cardiomyocyte-specific disruption of the Serca2 gene in adult mice were compared with Sercaflox/flox (FF) control mice. Six days after Serca2 gene disruption, SERCA2 protein abundance was reduced by 53% in KO compared with FF, whereas SERCA2 activity in field-stimulated, Fluo-5F AM-loaded cells was reduced by 42%. Baseline Ca 2+ content of the sarcoplasmic reticulum (SR) and Ca2+ transient amplitude and rate constant of decay measured in whole-cell voltage-clamped cells were decreased in KO to 75, 81, and 69% of FF values. Ca2+ waves developed in only 31% of KO cardiomyocytes compared with 57% of FF when external Ca2+ was raised (10 mM), although SR Ca 2+ content needed for waves to develop was 79% of FF values. In addition, waves propagated at a 15% lower velocity in KO cells. Ventricular extrasystoles (VES) occurred with lower frequency in SERCA2 KO mice (KO: 3 ± 1 VES/h vs. FF: 8 ± 1 VES/h) (P <0.05 for all results). Conclusion: Reduced SERCA2 abundance resulted in decreased amplitude and decay rate of Ca2+ transients, reduced SR Ca2+ content, and decreased propensity for Ca2+ wave development. © The Author 2009.
    Original languageEnglish
    Pages (from-to)63-71
    Number of pages8
    JournalCardiovascular research
    Issue number1
    Publication statusPublished - Apr 2010


    • Arrhythmias
    • Calcium waves
    • Delayed afterdepolarization
    • Excitation-contraction coupling
    • SERCA2


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