Cited 16 times since 2010 (1.2 per year) source: EuropePMC Journal of cardiovascular electrophysiology, Volume 21, Issue 11, 1 1 2010, Pages 1284-1292 Electrical activation of sinus venosus myocardium and expression patterns of RhoA and Isl-1 in the chick embryo. 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
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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.
