Conduction slowing by the gap junctional uncoupler carbenoxolone.

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Pharmacology

Background:

• Cellular electrical coupling is vital for cardiac action potential propagation; reduced coupling is linked to arrhythmias.
• Existing cellular uncoupling agents can cause detrimental side effects on membrane ionic currents.
• The study investigates carbenoxolone's impact on electrical coupling, ionic currents, and cardiac conduction.

Purpose of the Study:

• To determine the effect of carbenoxolone on cellular electrical coupling.
• To assess carbenoxolone's influence on membrane ionic currents in cardiac myocytes.
• To evaluate carbenoxolone's impact on atrial and ventricular conduction velocity in the heart.

Main Methods:

• Isolated rabbit ventricular and atrial myocytes were used to assess action potential characteristics and ionic currents.
• Dual current clamp experiments on cell pairs measured coupling conductance changes.
• High-density activation mapping in intact rabbit hearts evaluated electrograms and conduction velocity.

Main Results:

• Carbenoxolone (50 µmol/l) did not affect action potential characteristics or major ionic currents (calcium, potassium, sodium).
• Coupling conductance in poorly coupled cell pairs decreased by 21% (p<0.05).
• Carbenoxolone significantly reduced longitudinal and transversal conduction velocity in both ventricle and atrium (p<0.05).

Conclusions:

• Carbenoxolone induces cellular uncoupling, leading to slowed atrial and ventricular conduction.
• Cardiac membrane ionic currents are unaffected by carbenoxolone-induced uncoupling.
• Activation delay is exacerbated in poorly coupled cardiac tissue.