Characterization of the Hyperpolarization-Activated Current, I f , in Ventricular Myocytes From Human Failing Heart

Abstract

Background Disease-associated electrophysiological alterations may contribute to the increased predisposition to arrhythmias of the hypertrophied or failing myocardium. An I f -like current is expressed in rat left 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 undergoing 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 increasing inward current elicited on hyperpolarization. Membrane capacitance was 244±27 pF (n=25). I f occurred in all cells tested; its density 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; midpoint, −70.9±2.1 mV; slope, −5.4±0.3 mV; and maximal specific conductance, 19.6±2.5 pS/pF. I f blockade by extracellular cesium was voltage 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. Conclusions I f is present in human LVMs. Its electrophysiological characteristics resemble those previously described in hypertrophied rat LVMs and suggest that I f could be an arrhythmogenic mechanism in patients with severe heart failure.