A hyperpolarization-activated inward current in human myocardial cells

Normally-polarized tissue from the human atrial myocardium usually exhibits a diastolic depolarization phase which can be suppressed reversibly by Cs+ or enhanced by inhibiting the inward rectifier K+ current, iK1, with Ba2+. (Escande et al., 1986). Because the suppression of the diastolic slope by Cs+ leads to a hyperpolarization of the cell membrane at the end of the diastolic phase, it was suggested that Cs+ might inhibit an inward current responsible for diastolic depolarization. Among the ionic mechanisms underlying the diastolic depolarization phase of cardiac tissues, the hyperpolarization-activated inward current, if, fits well to explain the small diastolic slope of human atrial fibres. In other preparations, this inward current carried both by Na+ and K+ ions is rapidly deactivated during the action potential and entirely blocked by millimolar concentrations of Cs+ (DiFrancesco 1981; DiFrancesco, et al., 1986; Kokubun et al., 1982; Callewaert et al., 1984; Denyer and Brown, 1990). Such a current in human myocardial cells has not been characterized so far although its existence in human atrial trabeculae was previously reported in an abstract (Carmeliet, 1984). In the present study, we describe an inward current which activates upon hyperpolarization in patch-clamped single human atrial cells and shares similar characteristics with the if pacemaker current described in unicellular and intact preparations of mammalian cardiac tissues.