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

Abstract

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 IK1 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 IK1 (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 I(f) in mammalian pacemaker cells. The relative current size of I(f) and IK1 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.