Decreased ATP-sensitive K(+) current density during chronic human atrial fibrillation

Area of Science:

• Cardiology
• Electrophysiology
• Molecular Biology

Background:

• Chronic atrial fibrillation (AF) is associated with altered atrial myocyte action potential duration (APD).
• The role of ATP-sensitive potassium channels (I(K,ATP)) in the electrical remodeling of chronic AF remains largely unknown.
• Increased I(K,ATP) activity could shorten APD, potentially promoting AF initiation and maintenance.

Purpose of the Study:

• To investigate the activity of ATP-sensitive potassium channels (I(K,ATP)) in atrial myocytes from patients with chronic atrial fibrillation (AF) compared to those with sinus rhythm (SR).
• To determine if alterations in I(K,ATP) contribute to the electrical remodeling observed in chronic AF.

Main Methods:

• Human atrial myocytes were isolated from patients undergoing open-heart surgery (AF and SR groups).
• Whole-cell patch-clamp technique was used to measure inward rectifier currents, including I(K,ATP) activated by rilmakalim.
• I(K,ATP) and I(K1) currents were identified by their sensitivity to Ba(2+).

Main Results:

• No significant difference in I(K1) current density was observed between AF and SR groups.
• Rilmakalim dose-dependently activated I(K,ATP) in both AF and SR cells.
• Maximum I(K,ATP) activation was significantly smaller in AF cells compared to SR cells, indicating downregulation in chronic AF.
• Aortic valve disease and pulmonary hypertension were identified as independent contributors to I(K,ATP) current density.

Conclusions:

• Chronic atrial fibrillation is associated with a downregulation of ATP-sensitive potassium (I(K,ATP)) currents in atrial myocytes.
• This downregulation of I(K,ATP) represents a novel molecular mechanism contributing to electrical remodeling in chronic AF.
• Further research is warranted to explore the therapeutic implications of targeting I(K,ATP) in AF management.