P536Developing right bundle branch block in connexin40 deficient mice during prenatal development

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Abstract

Connexin40 (Cx40) is a major gap junction protein expressed in His-Purkinje system. In adult mice lacking Cx40, several changes in conductance have been described. ECG measurements of adult Cx40 knock-out mice showed pattern similar to right bundle branch (RBB) block. Endocardial ventricular conduction measurements suggested slowed conduction in RBB.

In our study, we focused on the impact of Cx40 deficiency on development of murine His-Purkinje system. We used optical mapping at different embryonic stages of Cx40 deficient mice and compared them with results from Cx40( + /-) mice and WT mice.

We found no major difference between examined groups in ventricular activation patterns or activation times at the early stages (ED 12.5 and ED 14.5) of distal conduction system development. In later stages of embryonic growth (ED 16.5 and ED 18.5) decreasing functionality of RBB was found, which was demonstrated by absence of epicardial breakthrough near the apex of the right ventricle. LBB activation was not affected; nevertheless there was significant increase in activation times of left ventricle in Cx40 deficient mice at these stages.

We suggest that in the early stages of development the function of bundle branches is dependent more on their morphological characteristics than on the intercellular coupling. The right bundle branch is morphologically smaller then left bundle branch, so we suggest that is more severely affected by Cx40 absence, while in LBB the Cx40 function is substituted by other, more slowly conducting, connexins (which corresponds with slowed activation times of left ventricular activation at later stages).

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