Initiation of embryonic cardiac pacemaker activity by inositol 1,4,5-trisphosphate-dependent calcium signaling

Annabelle Méry; Franck Aimond; Claudine Ménard; Katsuhiko Mikoshiba; Marek Michalak; Michel Pucéat

doi:10.1091/mbc.e04-10-0883

Initiation of embryonic cardiac pacemaker activity by inositol 1,4,5-trisphosphate-dependent calcium signaling

Mol Biol Cell. 2005 May;16(5):2414-23. doi: 10.1091/mbc.e04-10-0883. Epub 2005 Mar 9.

Authors

Annabelle Méry¹, Franck Aimond, Claudine Ménard, Katsuhiko Mikoshiba, Marek Michalak, Michel Pucéat

Affiliation

¹ CRBM, Centre National de la Recherche Scientifique FRE2593, 34293 Montpellier, France.

Abstract

In the adult, the heart rate is driven by spontaneous and repetitive depolarizations of pacemaker cells to generate a firing of action potentials propagating along the conduction system and spreading into the ventricles. In the early embryo before E9.5, the pacemaker ionic channel responsible for the spontaneous depolarization of cells is not yet functional. Thus the mechanisms that initiate early heart rhythm during cardiogenesis are puzzling. In the absence of a functional pacemaker ionic channel, the oscillatory nature of inositol 1,4,5-trisphosphate (InsP3)-induced intracellular Ca2+ signaling could provide an alternative pacemaking mechanism. To test this hypothesis, we have engineered pacemaker cells from embryonic stem (ES) cells, a model that faithfully recapitulates early stages of heart development. We show that InsP3-dependent shuttle of free Ca2+ in and out of the endoplasmic reticulum is essential for a proper generation of pacemaker activity during early cardiogenesis and fetal life.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium Channels / genetics
Calcium Channels / metabolism
Calcium Signaling / drug effects
Calcium Signaling / physiology*
Calreticulin / genetics
Calreticulin / metabolism
Clone Cells
DNA, Complementary / genetics
Endoplasmic Reticulum / metabolism
Fetal Heart / embryology*
Fetal Heart / metabolism*
Heart Conduction System / embryology*
Heart Conduction System / metabolism*
Inositol 1,4,5-Trisphosphate / metabolism*
Inositol 1,4,5-Trisphosphate / pharmacology
Inositol 1,4,5-Trisphosphate Receptors
Mice
Models, Cardiovascular
Myoblasts, Cardiac / drug effects
Myoblasts, Cardiac / metabolism
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism

Substances

Calcium Channels
Calreticulin
DNA, Complementary
Inositol 1,4,5-Trisphosphate Receptors
Receptors, Cytoplasmic and Nuclear
Recombinant Proteins
Inositol 1,4,5-Trisphosphate