The Journal of General Physiology
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Published online September 15, 2008
doi:10.1085/jgp.200809960
The Journal of General Physiology, Vol. 132, No. 4, 397-405
The Rockefeller University Press, 0022-1295 $30.00
© 2008 Rapila et al.
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 Excitation–Contraction Coupling of the Mouse Embryonic Cardiomyocyte



Risto Rapila, Topi Korhonen, and Pasi Tavi

Institute of Biomedicine, Department of Physiology and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland

Correspondence to Pasi Tavi: pasi.tavi{at}oulu.fi

In the mammalian embryo, the primitive tubular heart starts beating during the first trimester of gestation. These early heartbeats originate from calcium-induced contractions of the developing heart muscle cells. To explain the initiation of this activity, two ideas have been presented. One hypothesis supports the role of spontaneously activated voltage-gated calcium channels, whereas the other emphasizes the role of Ca2+ release from intracellular stores initiating spontaneous intracellular calcium oscillations. We show with experiments that both of these mechanisms coexist and operate in mouse cardiomyocytes during embryonic days 9–11. Further, we characterize how inositol-3-phosphate receptors regulate the frequency of the sarcoplasmic reticulum calcium oscillations and thus the heartbeats. This study provides a novel view of the regulation of embryonic cardiomyocyte activity, explaining the functional versatility of developing cardiomyocytes and the origin and regulation of the embryonic heartbeat.

Abbreviations used in this paper: AM, acetoxymethyl; AP, action potential; E–C, excitation–contraction; If, hyperpolarization-activated current; IP3, inositol-3-phosphate; IP3R, IP3 receptor; NCX, NA+/Ca2+ exchanger; RyR, ryanodine receptor; SL, sarcolemmal; VACC, voltage-activated calcium channel; Vm, membrane voltage.

© 2008 Rapila et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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Mathematical Model of Mouse Embryonic Cardiomyocyte Excitation–Contraction Coupling
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R. Rapila, T. Korhonen, and P. Tavi
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T. Korhonen, R. Rapila, and P. Tavi
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