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.

journal_name

Circulation

journal_title

Circulation

authors

Cerbai E,Pino R,Porciatti F,Sani G,Toscano M,Maccherini M,Giunti G,Mugelli A

doi

10.1161/01.cir.95.3.568

subject

Has Abstract

pub_date

1997-02-04 00:00:00

pages

568-71

issue

3

eissn

0009-7322

issn

1524-4539

journal_volume

95

pub_type

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