(Circulation. 1997;95:568-571.)
© 1997 American Heart Association, Inc.
Articles |
Characterization of the Hyperpolarization-Activated Current, If, in Ventricular Myocytes From Human Failing Heart
the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
Correspondence to Alessandro Mugelli, MD, Department of Preclinical and Clinical Pharmacology, University of Firenze, Viale G.B. Morgagni 65, 50134 Firenze, Italy. E-mail mugelli@stat.ds.unifi.it.
Background Disease-associated electrophysiological alterations may contribute to the increased predisposition to arrhythmias of the hypertrophied or failing myocardium. An If-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 If 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 If, ie, a barium-insensitive, cesium-sensitive, time-dependent increasing inward current elicited on hyperpolarization. Membrane capacitance was 244±27 pF (n=25). If occurred in all cells tested; its density measured at -120 mV was 2.1±0.3 pA/pF. Activation curves of If (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. If 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 If is present in human LVMs. Its electrophysiological characteristics resemble those previously described in hypertrophied rat LVMs and suggest that If could be an arrhythmogenic mechanism in patients with severe heart failure.
Key Words: arrhythmia • electrophysiology • myocytes • heart failure • hypertrophy
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