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 microM) 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(+)/Ca(2+) exchange current and Ca(2+) 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.
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 microM) 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(+)/Ca(2+) exchange current and Ca(2+) 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.
Authors: Márcia Vagos; Ilsbeth G M van Herck; Joakim Sundnes; Hermenegild J Arevalo; Andrew G Edwards; Jussi T Koivumäki Journal: Front Physiol Date: 2018-09-04 Impact factor: 4.566