Chamber-related differences in connexin expression in the human heart

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Cellular Electrophysiology

Background:

• Electrical coupling in the heart relies on gap junctions formed by connexins.
• Connexin43 (Cx43) is the primary cardiac connexin, often reduced in arrhythmias.
• Expression patterns of other cardiac connexins (Cx40, Cx45, Cx37) in the human heart are not fully understood.

Purpose of the Study:

• To comprehensively analyze and compare the mRNA and protein expression of Cx43, Cx40, Cx37, and Cx45 in human atrial and ventricular chambers.
• To elucidate chamber-specific connexin expression profiles in the healthy human heart.

Main Methods:

• Northern blotting to assess mRNA expression.
• Western blotting to evaluate protein levels.
• Immunoconfocal microscopy for cellular localization of connexins.

Main Results:

• Connexin43 (Cx43) was uniformly abundant across all four heart chambers (left ventricle, right ventricle, left atrium, right atrium).
• Connexin40 (Cx40) expression varied significantly, with higher levels in the right atrium, followed by the left atrium, then ventricles.
• Connexin37 (Cx37) showed consistent expression in the endothelium of all chambers, while Cx45 was detected at low levels, trending higher in atria than ventricles.

Conclusions:

• Human atria and ventricles exhibit distinct connexin expression profiles, with the right atrium showing a more pronounced atrial profile.
• Ventricular connexin patterns are conserved across mammalian species, but atrial expression displays greater interspecies variation.
• These findings provide a framework for understanding the role of altered connexin expression in human ventricular and atrial arrhythmias.