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

Objective: The hyperpolarization-activated inward current (I-f) 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 I-f. In the present study, we evaluate characteristics of I-f 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 I-f in isolated myocytes from 96 human right atrial appendages. I-f 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 I-f activation by +7 mV (7/7) using the perforated-patch technique, but only inconsistently shifted I-f activation using the ruptured-patch method (6/21). Based on the relative current size of I-f and I-K1 three cell types could be distinguished (n = 26). In myocytes with a prominent I-f, I-f 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 I-K1 (in [K+](o) 25 mmol/l at -80 mV: -0.02 +/- 0.01 pApF(-1); n = 4) (P < 0.05). Conclusions: I-f 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 I-f and I-K1 were found to be variable in different myocytes. Whether I-f may favor spontaneous diastolic depolarization in individual human atrial myocytes exhibiting predominantly I-f in vivo remains to be defined, as current size is very small under physiological [K+](o). (C) 1998 Elsevier Science B.V. All rights reserved.