High resolution optical mapping reveals conduction slowing in connexin43 deficient mice

Area of Science:

• Cardiovascular Physiology
• Molecular Cardiology
• Genetics

Background:

• Cardiac connexins, like connexin43 (Cx43), are crucial for cell-to-cell communication and impulse propagation in the heart.
• Previous studies on Cx43 heterozygous mice (Cx43+/-) yielded conflicting results regarding cardiac conduction velocity.
• Understanding Cx43's role is vital for insights into arrhythmias and heart function.

Purpose of the Study:

• To investigate the impact of reduced connexin43 (Cx43) expression on cardiac impulse propagation.
• To resolve discrepancies in previous findings on conduction velocity in Cx43 heterozygous mice.
• To evaluate the utility of high-resolution optical mapping in studying cardiac electrophysiology in genetically modified models.

Main Methods:

• High-resolution optical mapping of ventricular action potentials in Langendorff-perfused hearts from Cx43+/- and wildtype mice.
• Development of a sensitive method to measure epicardial conduction velocity, minimizing artifacts.
• Quantification of Cx43 protein expression and analysis of action potential duration.

Main Results:

• Epicardial conduction velocity was significantly reduced (23-35%) in Cx43+/- mice compared to wildtype controls (P<0.01).
• Conduction patterns and anisotropy remained unchanged, indicating uniform Cx43 reduction.
• Cx43 protein expression was reduced by approximately 45% in heterozygotes, consistent across different genetic backgrounds.

Conclusions:

• A ~50% reduction in Cx43 expression demonstrably slows cardiac conduction velocity in mice.
• Discrepancies in prior studies may stem from technical limitations rather than genetic background differences.
• High-resolution optical mapping is an effective tool for elucidating molecular influences on cardiac propagation and arrhythmias.