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Cardiovascular Research 1998 38(3):788-801; doi:10.1016/S0008-6363(98)00047-9
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Characterization of the hyperpolarization-activated inward current in isolated human atrial myocytes

Uta C Hoppe* and Dirk J Beuckelmann

Department of Medicine III, University of Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany

* Corresponding author. Tel.: +49 (221) 478-3138; Fax: +49 (221) 478-3163.

Objective: The hyperpolarization-activated inward current (If) has been discussed to contribute to arrhythmias in rat hypertrophied and human failing ventricular myocardium. Cat atrial myocytes were found to exhibit variable size of If. In the present study, we evaluate characteristics of If in human atrial myocardium and investigate if human atria might exhibit any electrophysiological heterogeneity in the diastolic voltage range. Methods and results: The whole-cell patch-clamp technique was used to record If in isolated myocytes from 96 human right atrial appendages. If was observed in 95% (ruptured-patch; 141/146) to 100% (perforated-patch; 18/18) of myocytes showing typical current properties, i.e. time- and voltage-dependence, block by [Cs+]o, permeability for K+, Na+ and Li+, and current increase with raising [K+]o. Using the perforated-patch technique Boltzmann distributions yielded an activation threshold of –60 to –70 mV and half maximal activation at –89.3±0.7 mV (n=18). Isoproterenol (10–6 mol/l) shifted If activation by +7 mV (7/7) using the perforated-patch technique, but only inconsistently shifted If activation using the ruptured-patch method (6/21). Based on the relative current size of If and IK1 three cell types could be distinguished (n=26). In myocytes with a prominent If, If density was found to be larger (in [K+]o 25 mmol/l at –80 mV: –0.78±0.23 pApF–1; n=7) than in cells with predominant IK1 (in [K+]o 25 mmol/l at –80 mV: –0.02±0.01 pApF–1; n=4) (P<0.05). Conclusions: If is present in most human atrial myocytes. Many current properties are similar to those described for If in mammalian pacemaker cells. The relative current size of If and IK1 were found to be variable in different myocytes. Whether If may favor spontaneous diastolic depolarization in individual human atrial myocytes exhibiting predominantly If in vivo remains to be defined, as current size is very small under physiological [K+]o.

KEYWORDS Ion channel; Pacemaker current; Patch clamp; Human atrial myocyte


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