If in left human atrium: a potential contributor to atrial ectopy.

Area of Science:

• Cardiology
• Electrophysiology
• Molecular Biology

Background:

• The left human atrium is implicated in atrial fibrillation (AF) initiation.
• The hyperpolarization-activated cation current (I(f)) is a potential contributor to abnormal automaticity in AF.
• Electrophysiological data on I(f) in the human left atrium were previously lacking.

Purpose of the Study:

• To investigate the presence and characteristics of I(f) in human left atrial tissue.
• To determine if I(f) can induce spontaneous activity in human atrial cells.

Main Methods:

• Isolation of human atrial myocytes from the left atrial appendage (LAA) and left atrial wall (LAW).
• Measurement of I(f) using whole-cell patch-clamp technique.
• Mathematical modeling of human atrial myocytes to simulate I(f) effects.

Main Results:

• Significantly higher I(f) densities were observed in LAA cells compared to LAW cells.
• I(f) activation potentials (V(1/2)) were less negative in LAA cells (-84.3 mV) than in LAW cells (-97.8 mV).
• Isoproterenol stimulation accelerated I(f) activation and shifted V(1/2) to more positive potentials in both regions.
• Mathematical models showed I(f) could induce spontaneous activity in quiescent atrial cells.

Conclusions:

• I(f) is present in human left atrial myocytes, with regional differences in its properties.
• I(f) current densities are sufficient to convert quiescent atrial cells into pacemaker cells.
• These findings support the role of I(f) in abnormal automaticity contributing to human atrial fibrillation.