The Journal of General Physiology
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Published online
doi:10.1085/jgp.200609575
The Journal of General Physiology, Vol. 130, No. 2, 133-144
The Rockefeller University Press, 0022-1295 $30.00
© Sasse et al.
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ARTICLE

 Intracellular Ca2+ Oscillations, a Potential Pacemaking Mechanism in Early Embryonic Heart Cells



Philipp Sasse1, Jianbao Zhang2,3, Lars Cleemann4, Martin Morad4, Juergen Hescheler2, and Bernd K. Fleischmann1

1 Institute of Physiology I, Life and Brain Center, University of Bonn, Bonn 53105, Germany
2 Institute of Neurophysiology, University of Cologne, Cologne 50931, Germany
3 Institute of Biomedical Engineering, Xi'an Jiaotong University, Xi'an 710049, China
4 Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057

Correspondence to Bernd K. Fleischmann: bernd.fleischmann{at}uni-bonn.de

Early (E9.5–E11.5) embryonic heart cells beat spontaneously, even though the adult pacemaking mechanisms are not yet fully established. Here we show that in isolated murine early embryonic cardiomyocytes periodic oscillations of cytosolic Ca2+ occur and that these induce contractions. The Ca2+ oscillations originate from the sarcoplasmic reticulum and are dependent on the IP3 and the ryanodine receptor. The Ca2+ oscillations activate the Na+-Ca2+ exchanger, giving rise to subthreshold depolarizations of the membrane potential and/or action potentials. Although early embryonic heart cells are voltage-independent Ca2+ oscillators, the generation of action potentials provides synchronization of the electrical and mechanical signals. Thus, Ca2+ oscillations pace early embryonic heart cells and the ensuing activation of the Na+-Ca2+ exchanger evokes small membrane depolarizations or action potentials.

Abbreviations used in this paper: AP, action potential; CICR, Ca2+-induced Ca2+ release; ES, embryonic stem; FFT, fast Fourier transformation; IP3, inositol-1,4,5-trisphosphate; IP3R, IP3 receptor; MDP, maximum diastolic potential; NCX, Na+-Ca2+ exchanger; TTX, tetrodotoxin; 2-APB, 2-aminoethyl diphenyl borate.


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