Slow ventricular conduction in mice heterozygous for a connexin43 null mutation

Area of Science:

• Cardiovascular Physiology
• Molecular Cardiology
• Genetics

Background:

• Gap junction protein connexin43 (Cx43) is vital for cardiac electrical impulse propagation.
• Understanding Cx43's role in ventricular conduction is critical for diagnosing and treating heart rhythm disorders.

Purpose of the Study:

• To investigate the functional impact of connexin43 (Cx43) gene deletion on ventricular conduction.
• To characterize the electrophysiological consequences of reduced Cx43 expression in the heart.

Main Methods:

• Utilized genetically modified mice with targeted deletion of the Cx43 gene (Cx43 -/- and Cx43 -/+).
• Measured ventricular epicardial conduction velocity in neonatal and adult mice using electrophysiological recordings.
• Performed electrocardiogram (ECG) analysis to assess cardiac electrical activity.
• Analyzed action potential parameters in cultured ventricular myocytes.

Main Results:

• Homozygous Cx43 knockout mice (Cx43 -/-) exhibited non-viability shortly after birth.
• Heterozygous Cx43 knockout mice (Cx43 -/+) showed significantly slowed ventricular epicardial conduction velocity (30% in neonates, 44% in adults) compared to wild-type littermates.
• Adult Cx43 -/+ mice displayed prolonged QRS complex duration on ECGs.
• No significant differences in action potential parameters were observed in isolated ventricular myocytes.

Conclusions:

• Targeted reduction of Cx43 abundance directly impairs ventricular conduction velocity.
• Cx43 plays a critical role in maintaining normal cardiac electrical propagation.
• Altered Cx43 expression is linked to significant electrophysiological abnormalities in the heart.