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Calcium waves driven by "sensitization” wave-fronts

Keller, Markus ; Kao, Joseph P.Y. ; Egger, Marcel ; Niggli, Ernst

In: Cardiovascular Research, 2007, vol. 74, no. 1, p. 39-45

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    Titel
    • Calcium waves driven by "sensitization” wave-fronts
    Autor
    • Keller, Markus. Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland
    • Kao, Joseph P.Y.. Medical Biotechnology Center, University of Maryland Biotechnology Institute and Department of Physiology, University of Maryland School of Medicine, Baltimore, USA
    • Egger, Marcel. Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland
    • Niggli, Ernst. Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland
    Dokumententyp
    • Postprint
    OAI-PMH-ID
    • oai:doc.rero.ch:304537
    Summary
    Objective: Cellular Ca2+ waves are understood as reaction-diffusion systems sustained by Ca2+-induced Ca2+ release (CICR) from Ca2+ stores. Given the recently discovered sensitization of Ca2+ release channels (ryanodine receptors; RyRs) of the sarcoplasmic reticulum (SR) by luminal SR Ca2+, waves could also be driven by RyR sensitization, mediated by SR overloading via Ca2+ pump (SERCA), acting in tandem with CICR. Methods: Confocal imaging of the Ca2+ indicator fluo-3 was combined with UV-flash photolysis of caged compounds and the whole-cell configuration of the patch clamp technique to carry out these experiments in isolated guinea pig ventricular cardiomyocytes. Results: Upon sudden slowing of the SERCA in cardiomyocytes with a photoreleased inhibitor, waves indeed decelerated immediately. No secondary changes of Ca2+ signaling or SR Ca2+ content due to SERCA inhibition were observed in the short time-frame of these experiments. Conclusions: Our findings are consistent with Ca2+ loading resulting in a zone of RyR ‘sensitization' traveling within the SR, but inconsistent with CICR as the predominant mechanism driving the Ca2+ waves. This alternative mode of RyR activation is essential to fully conceptualize cardiac arrhythmias triggered by spontaneous Ca2+ release