Electrical activation of sinus venosus myocardium and expression patterns of RhoA and Isl-1 in the chick embryo.

Abstract:

UNLABELLED:Electrical Activity and RhoA in the Embryo. INTRODUCTION:Myocardium at the venous pole (sinus venosus) of the heart has gained clinical interest as arrhythmias can be initiated from this area. During development, sinus venosus myocardium is incorporated to the primary heart tube and expresses different markers than primary myocardium. We aimed to elucidate the development of sinus venosus myocardium, including the sinoatrial node (SAN), by studying expression patterns of RhoA in relation to other markers, and by studying electrical activation patterns of the developing sinus venosus myocardium. METHODS AND RESULTS:Expression of RhoA, myocardial markers cTnI and Nkx2.5, transcription factors Isl-1 and Tbx18, and cation channel HCN4 were examined in sequential stages in chick embryos. Electrical activation patterns were studied using microelectrodes and optical mapping. Embryonic sinus venosus myocardium is cTnI and HCN4 positive, Nkx2.5 negative, complemented by distinct patterns of Isl-1 and Tbx18. During development, initial myocardium-wide expression of RhoA becomes restricted to right-sided sinus venosus myocardium, comprising the SAN. Electrophysiological measurements revealed initial capacity of both atria to show electrical activity that in time shifts to a right-sided dominance, coinciding with persistence of RhoA, Tbx18, and HCN4 and absence of Nkx2.5 expression in the definitive SAN. CONCLUSION:Results show an initially bilateral electrical potential of sinus venosus myocardium evolving into a right-sided activation pattern during development, and suggest a role for RhoA in conduction system development. We hypothesize an initial sinus venosus-wide capacity to generate pacemaker signals, becoming confined to the definitive SAN. Lack of differentiation toward a chamber phenotype would explain ectopic pacemaker foci.

authors

Vicente-Steijn R,Kolditz DP,Mahtab EA,Askar SF,Bax NA,VAN DER Graaf LM,Wisse LJ,Passier R,Pijnappels DA,Schalij MJ,Poelmann RE,Gittenberger-DE Groot AC,Jongbloed MR

doi

10.1111/j.1540-8167.2010.01790.x

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

1284-92

issue

11

eissn

1045-3873

issn

1540-8167

pii

JCE1790

journal_volume

21

pub_type

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