Connexin 43 expression delineates two discrete pathways in the human atrioventricular junction

Area of Science:

• Cardiovascular Biology
• Cardiac Electrophysiology
• Molecular Cardiology

Background:

• Gap junction expression, specifically connexin 43 (Cx43), is crucial for cardiac conduction.
• While studied in other species, Cx43 distribution within the human atrioventricular junction (AVJ) remains largely uncharacterized.
• Species-dependent variations in Cx43 expression necessitate direct investigation in humans.

Purpose of the Study:

• To investigate and map the distribution of the gap junction protein Cx43 within the human AVJ.
• To determine the cellular origin of Cx43 expression in the human AVJ.
• To correlate Cx43 expression patterns with potential functional implications for cardiac conduction and arrhythmias.

Main Methods:

• Three-dimensional reconstruction of the human AVJ using Masson trichrome histology.
• Immunolabeling for Cx43, vimentin, and alpha-actinin to identify cellular sources.
• Quantitative analysis of Cx43 expression in distinct AVJ structures (IAS, His bundle, CN, LNB, LE, RE) and transitional cells.

Main Results:

• Cx43 was localized to myocytes, not fibroblasts, within the human AVJ.
• Distinct Cx43 expression patterns were observed: lower levels in the leftward extension (LE) and compact node (CN), and moderate levels (approx. 50% of interatrial septum) in the rightward extension (RE), lower nodal bundle (LNB), and His bundle.
• Transitional cell Cx43 levels were comparable to the interatrial septum.

Conclusions:

• The human AVJ exhibits differential Cx43 expression, delineating two functional pathways: one with low Cx43 (LE, CN) and another with moderate Cx43 (His, LNB, RE).
• This heterogeneous Cx43 distribution likely confers unique electrical properties to different AVJ segments.
• Variations in Cx43 expression may underlie the development of AVJ-related arrhythmias.