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


BACKGROUND
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.


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.


CONCLUSIONS
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.
Vicente-Steijn
Rebecca
R
Department of Anatomy and Embryology Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Kolditz
Denise P
DP
Mahtab
Edris A F
EA
Askar
Saïd F A
SF
Bax
Noortje A M
NA
VAN DER Graaf
Linda M
LM
Wisse
Lambertus J
LJ
Passier
Robert
R
Pijnappels
Daniël A
DA
Schalij
Martin J
MJ
Poelmann
Robert E
RE
Gittenberger-DE Groot
Adriana C
AC
Jongbloed
Monique R M
MR
D000200:Action Potentials; D000818:Animals; D016275:Atrial Function / Q000502:physiology*; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006329:Heart Conduction System / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D020742:rhoA GTP-Binding Protein