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Cardiovascular Research 2007 74(1):39-45; doi:10.1016/j.cardiores.2007.02.006
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Copyright © 2007, European Society of Cardiology

Calcium waves driven by "sensitization" wave-fronts

Markus Kellera, Joseph P.Y. Kaob, Marcel Eggera and Ernst Nigglia,*

aDepartment of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland
bMedical Biotechnology Center, University of Maryland Biotechnology Institute and Department of Physiology, University of Maryland School of Medicine, Baltimore, USA

* Corresponding author. Tel.: +41 31 631 8730; fax: +41 631 4611. Email address: niggli{at}pyl.unibe.ch

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.

KEYWORDS Calcium; SR; Ca2+ pump; Myocytes; Ec-coupling

Time for primary review 11 days


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