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

Objective: The left human atrium plays an important role in initiation of atrial fibrillation (AF) and the hyperpolarization activated cation current (I-f) is a candidate for contributing to abnormal automaticity. However, electrophysiological data concerning I-f are not available in this cardiac region and we therefore investigated I-f in human left atrial tissue. Methods: Human atrial myocytes were isolated from the left atrial appendage (LAA) and the left atrial wall (LAW) obtained from patients undergoing open heart surgery. I-f was measured with the whole-cell patch-clamp technique. Results: I-f densities between -70 and -110 mV were found to be significantly higher in LAA than in LAW cells. Furthermore, in the group of LAA cells the half maximal activation potential (V-1/2) was found to be less negative (V-1/2 of -84.3 +/- 1.9 mV, n = 14/9) compared to LAW Cells (V-1/2 of -97.8 +/- 2.1 mV, n = 28/9). Beta-adrenergic receptor Stimulation with isoproterenol (1 muM) caused an acceleration of current activation and a V-1/2 shift to more positive potentials in cells of both regions (LAA: 8.8 +/- 2.3 mV, n = 6/4 and LAW: 8.9 +/- 2.6 mV, n = 6/4). Simulations using a mathematical model of the human atrial myocyte demonstrated that I-f was able to induce spontaneous activity in the model at a regular rhythm due to the interplay of I-f, Na+/Ca2+ exchange current and Ca2+ release of the sarcoplasmic reticulum (SR). Conclusions: Our study revealed the presence of I-f in left atrial myocytes and showed that I-f parameters depend on atrial region. I-f current densities were sufficient to convert the mathematical model of a quiescent human atrial cell into a pacemaker cell. These data support the hypothesis of I-f as a contributor to abnormal automaticity in human atrial tissue. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.