From the Departments of Medicine III (U.C.H., E.J., D.J.B.) and
Cardiovascular Surgery (M.S.), University of Cologne, Germany.
Correspondence to Uta C. Hoppe, MD, Department of Medicine III, University of Cologne, Joseph-Stelzmann-Str 9, 50924 Cologne, Germany. E-mail dirk.beuckelmann{at}uni-koeln.de
Background—The
hyperpolarization-activated inward current
(If) was found to be overexpressed in hypertrophied rat
ventricular myocytes, indicating that If might
favor arrhythmias in hypertrophied or failing
ventricular myocardium. In the present
study, we evaluated whether If is expressed in human
ventricular myocardium, if it may be increased
in human heart failure, and if its autonomic modulation may be
altered.
Methods and Results—The whole-cell patch-clamp technique was used
to record If in isolated ventricular
myocytes from 34 failing (dilated [DCM] or ischemic [ICM]
cardiomyopathy) and 13 donor hearts (NF).
If was observed in all myocytes showing typical current
properties, ie, time and voltage dependence, block by
[Cs+]o, permeability for K+ and
Na+, and current increase with raising
[K+]o. There was a trend toward larger
current densities in myopathic (at -130 mV in
[K+]o 25 mmol/L; DCM: -1.37±0.12
pA/pF, n=50; ICM: -1.39±0.24 pA/pF, n=30) than in nonfailing cells
(-1.18±0.21 pA/pF, n=24), although this difference did not reach
statistical significance (P=.23). Boltzmann
distributions yielded an activation threshold of -80 mV and
half-maximal activation at -110.96±0.06 mV in myopathic and normal
myocytes. Isoproterenol (10-5 mol/L) shifted the current
activation by 10 mV (31 myopathic, 5 NF). Carbachol and
adenosine had no direct effect on If (6 and 12
myopathic, 3 and 3 NF, respectively) but reversibly antagonized
ß-adrenergic stimulation (5 and 7 myopathic, 2 and 2 NF,
respectively). Autonomic modulation was similar in failing and
nonfailing cells.
Conclusions—In end-stage heart failure, no significant change of
If could be found, although there was a trend toward
increased If. Together with an elevated plasma
norepinephrine concentration and a previously reported
reduction in IK1 in human heart failure, If
might favor diastolic depolarization in individual
myopathic cells.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Hyperpolarization-Activated Inward Current in Ventricular Myocytes From Normal and Failing Human Hearts
Key Words: electrophysiology • heart failure • ventricles • adenosine • arrhythmia
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