Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles. This system may have evolved together with high heart rates to support their endothermic state (warm-bloodedness) and is seemingly lacking in ectothermic vertebrates from which first mammals then birds independently evolved. Here, we studied the conduction system in crocodiles (Alligator mississippiensis), the only ectothermic vertebrates with a full ventricular septum. We identified homologues of mammalian conduction system markers (Tbx3-Tbx5, Scn5a, Gja5, Nppa-Nppb) and show the presence of a functional atrioventricular bundle. The ventricular Purkinje network, however, was absent and slow ventricular conduction relied on trabecular myocardium, as it does in other ectothermic vertebrates. We propose the evolution of the atrioventricular bundle followed full ventricular septum formation prior to the development of high heart rates and endothermy. In contrast, the evolution of the ventricular Purkinje network is strongly associated with high heart rates and endothermy.

• MeSH
• aligátoři a krokodýli embryologie   genetika   fyziologie   MeSH
• embryo nesavčí metabolismus   MeSH
• Hisův svazek embryologie   metabolismus   fyziologie   MeSH
• hybridizace in situ MeSH
• mezikomorová přepážka embryologie   metabolismus   fyziologie   MeSH
• modely kardiovaskulární MeSH
• převodní systém srdeční embryologie   fyziologie   MeSH
• proteiny T-boxu genetika   metabolismus   MeSH
• Purkyňova vlákna embryologie   metabolismus   fyziologie   MeSH
• srdce embryologie   fyziologie   MeSH
• srdeční frekvence genetika   fyziologie   MeSH
• srdeční komory embryologie   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: The aim of this study was to characterize ventricular activation patterns in normal and connexin40-deficient mice in order to dissect the role of connexin40 in developing the conduction system. METHODS AND RESULTS: We performed optical mapping of epicardial activation between ED9.5-18.5 and analysed ventricular activation patterns and times of left ventricular activation. Mouse embryos deficient for connexin40 were compared with normal and heterozygous littermates. Morphology of the primary interventricular ring (PIR) was delineated with the help of T3-LacZ transgene. Four major types of ventricular activation patterns characterized by primary breakthrough in different parts of the heart were detected during development: PIR, left ventricular apex, right ventricular apex, and dual right and left ventricular apices. Activation through PIR was frequently present at the early stages until ED12.5. From ED14.5, the majority of hearts showed dual left and right apical breakthrough, suggesting functionality of both bundle branches. Connexin40-deficient embryos showed initially a delay in left bundle branch function, but the right bundle branch block, previously described in the adults, was not detected in ED14.5 embryos and appeared only gradually with 80% penetrance at ED18.5. CONCLUSION: The switch of function from the early PIR conduction pathway to the mature apex to base activation is dependent upon upregulation of connexin40 expression in the ventricular trabeculae. The early function of right bundle branch does not depend on connexin40. Quantitative analysis of normal mouse embryonic ventricular conduction patterns will be useful for interpretation of effects of mutations affecting the function of the cardiac conduction system.

• MeSH
• akční potenciály MeSH
• blokáda Tawarova raménka genetika   metabolismus   MeSH
• gestační stáří MeSH
• Hisův svazek embryologie   metabolismus   MeSH
• konexiny nedostatek   genetika   MeSH
• lac operon MeSH
• morfogeneze MeSH
• myši knockoutované MeSH
• myši transgenní MeSH
• myši MeSH
• penetrance MeSH
• převodní systém srdeční embryologie   metabolismus   MeSH
• srdeční komory embryologie   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zobrazování pomocí barviva citlivého na potenciál MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH