CHARACTERIZATION OF THE HYPERPOLARIZATION-ACTIVATED CURRENT, I-F, IN VENTRICULAR MYOCYTES FROM HUMAN FAILING HEART

Background Disease-associated electrophysiological alterations may con tribute to the increased predisposition to arrhythmias of the hypertro phied or failing myocardium. An I-f-like current is expressed in rat l eft ventricular myocytes (LVMs), its amplitude being linearly related to the severity of cardiac hypertrophy. Here, we report the occurrence and electrophysiological properties of I-f in human LVMs. Methods and Results LVMs were isolated from hearts of three male patients undergo ing cardiac transplantation for terminal heart failure due to ischemic dilated cardiomyopathy. The patch-clamp technique was used to record I-f, ie, a barium-insensitive, cesium-sensitive, time-dependent increa sing inward current elicited on hyperpolarization. Membrane capacitanc e was 244+/-27 pF (n=25). I-f occurred in all cells tested; its densit y measured at -120 mV was 2.1+/-0.3 pA/pF. Activation curves of I-f (n =24) were fitted by a Boltzmann function; the threshold was -55 mV; mi dpoint, -70.9+/-2.1 mV; slope, -5.4+/-0.3 mV; and maximal specific con ductance, 19.6+/-2.5 pS/pF. I-f blockade by extracellular cesium was v oltage dependent. Reducing extracellular potassium concentration from 25 to 5.4 mmol/L caused a shift of the reversal potential from -12.7+/ -0.5 to -24.8+/-2.1 mV and a 64% decrease of current conductance. Conc lusions I-f is present in human LVMs. Its electrophysiological charact eristics resemble those previously described in hypertrophied rat LVMs and suggest that I-f could be an arrhythmogenic mechanism in patients with severe heart failure.