Characterization of the hyperpolarization-activated current, I (f) , in ventricular myocytes from human failing heart
Cerbai, E.; Pino, R.; Porciatti, F.; Sani, G.; Toscano, M.; Maccherini, M.; Giunti, G.; Mugelli, A.
Circulation 95(3): 568-571
1997
ISSN/ISBN: 0009-7322 PMID: 9024140 Document Number: 477452
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.