RvD1 and LXA₄ inhibitory effects on cardiac voltage-gated potassium channels

Area of Science:

• Cardiovascular Physiology
• Molecular Pharmacology
• Electrophysiology

Background:

• Specialized pro-resolving lipid mediators (SPMs) resolve inflammation and can be altered in cardiovascular diseases.
• RvD1 and LXA4 are SPMs known to prevent atrial fibrillation (AF) remodeling and cardiac hypertrophy in animal models.
• Electrophysiological effects of RvD1 and LXA4 on cardiac voltage-gated (VG) ion channels remain largely unknown.

Purpose of the Study:

• To investigate the acute electrophysiological effects of RvD1 and LXA4 on cardiac VG potassium channels.
• To assess the impact of RvD1 and LXA4 on atrial and ventricular action potentials (APs) using in silico simulations.

Main Methods:

• Patch-clamp electrophysiology in heterologous systems and guinea-pig cardiomyocytes.
• Assessment of multiple VG potassium currents including IKs, IKur, Ito, IKr, and IK1.
• In silico modeling to predict AP changes.

Main Results:

• RvD1 significantly reduced IKs current in both cell types and showed potent inhibition of IKr.
• RvD1 was more potent than LXA4 in modulating potassium currents.
• In silico simulations predicted RvD1 prolongs repolarization in both atrial and ventricular myocytes.

Conclusions:

• RvD1 and LXA4 exert direct electrophysiological effects on cardiac potassium channels at relevant concentrations.
• RvD1's potent inhibition of potassium currents suggests a role in reversing AF-induced electrical remodeling.
• Further research is needed to confirm RvD1's effects on ventricular remodeling.