Development of the Cardiac Conduction System

Moorman, Antoon F.M.; Jong, F. De; Denyn, M. M. F. J.; Lamers, W. H.

doi:10.1161/01.res.82.6.629

Cited by 233 publications

(203 citation statements)

References 178 publications

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“…Compact and trabeculated myocardium are under distinct genetic control, have different myocardial properties, and express different levels of cardiac genes (Sucov et al, 1994;Gassmann et al, 1995;Meyer and Birchmeier, 1995;Franco et al, 1998;Moorman et al, 1998). The finding that the compact ventricular myocardium shows left and right chamber-specific transcriptional properties is consistent with the observation that the LV acquires a compact myocardial morphology before the RV (Ya et al, 1997).…”

Section: Discussionsupporting

confidence: 72%

Suppression of atrial myosin gene expression occurs independently in the left and right ventricles of the developing mouse heart

Zammit¹,

Kelly²,

Franco³

et al. 2000

Dev. Dyn.

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Section: Discussionsupporting

confidence: 72%

Suppression of atrial myosin gene expression occurs independently in the left and right ventricles of the developing mouse heart

Zammit¹,

Kelly²,

Franco³

et al. 2000

Dev. Dyn.

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“…Although most of them are the product of embryonic cardiac genes, a subset of proteins and epitopes is shared with neural tissue (31,43,44). Independent evidence for specific, neuronal-like protein expression is the observation that in newborn SAN, a neuronal type I fast sodium channel exists and is under developmental control (44).…”

Section: Discussionmentioning

confidence: 99%

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Moroni¹,

Gorza²,

Beltrame³

et al. 2001

Journal of Biological Chemistry

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The pacemaker current I f of the sinoatrial node (SAN) is a major determinant of cardiac diastolic depolarization and plays a key role in controlling heart rate and its modulation by neurotransmitters. Substantial expression of two different mRNAs (HCN4, HCN1) of the family of pacemaker channels (HCN) is found in rabbit SAN, suggesting that the native channels may be formed by different isoforms. Here we report the cloning and heterologous expression of HCN1 from rabbit SAN and its specific localization in pacemaker myocytes. rbHCN1 is an 822-amino acid protein that, in human embryonic kidney 293 cells, displayed electrophysiological properties similar to those of I f , suggesting that HCN1 can form a pacemaker channel. The presence of HCN1 in the SAN myocytes but not in nearby heart regions, and the electrophysiological properties of the channels formed by it, suggest that HCN1 plays a central and specific role in the formation of SAN pacemaker currents.

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“…RyR2 expression in developing myocardium however precedes the time when augmented heart function is critical to the continued development of the embryo (5). Because an increase in heart rate is critical to enhanced cardiac output as embryonic development proceeds (6)(7)(8), an understanding of the mechanisms that regulate heart rate during early cardiac development is needed.…”

mentioning

confidence: 99%

The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development

Huang

Tweedie

Wang

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

108

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In adult myocardium, the heartbeat originates from the sequential activation of ionic currents in pacemaker cells of the sinoatrial node. Ca 2؉ release via the ryanodine receptor (RyR) modulates the rate at which these cells beat. In contrast, the mechanisms that regulate heart rate during early cardiac development are poorly understood. Embryonic stem (ES) cells can differentiate into spontaneously contracting myocytes whose beating rate increases with differentiation time. These cells thus offer an opportunity to determine the mechanisms that regulate heart rate during development. Here we show that the increase in heart rate with differentiation is markedly depressed in ES cell-derived cardiomyocytes with a functional knockout (KO) of the cardiac ryanodine receptor (RyR2). KO myocytes show a slowing of the rate of spontaneous diastolic depolarization and an absence of calcium sparks. The depressed rate of pacemaker potential can be mimicked in wild-type myocytes by ryanodine, and rescued in KO myocytes with herpes simplex virus (HSV)-1 amplicons containing full-length RyR2. We conclude that a functional RyR2 is crucial to the progressive increase in heart rate during differentiation of ES cell-derived cardiomyocytes, consistent with a mechanism that couples Ca 2؉ release via RyR before an action potential with activation of an inward current that accelerates membrane depolarization.

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Development of the Cardiac Conduction System

Cited by 233 publications

References 178 publications

Suppression of atrial myosin gene expression occurs independently in the left and right ventricles of the developing mouse heart

Suppression of atrial myosin gene expression occurs independently in the left and right ventricles of the developing mouse heart

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development

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