Does the hyperpolarization-activated inward current (I[f]) differ in ventricular myocytes from failing versus nonfailing human hearts?
The hyperpolarization-activated inward current (I[f]) is present in human ventricular myocytes and shows a non-significant trend toward increased density in end-stage heart failure, which may contribute to arrhythmogenesis.
BACKGROUND: The hyperpolarization-activated inward current (If) was found to be overexpressed in hypertrophied rat ventricular myocytes, indicating that I(f) might favor arrhythmias in hypertrophied or failing ventricular myocardium. In the present study, we evaluated whether I(f) 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 I(f) in isolated ventricular myocytes from 34 failing (dilated DCM or ischemic ICM cardiomyopathy) and 13 donor hearts (NF). I(f) 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 I(f) (6 and 12 myopathic, 3 and 3 NF, respectively) but reversibly antagonized beta-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 I(f) could be found, although there was a trend toward increased I(f). Together with an elevated plasma norepinephrine concentration and a previously reported reduction in I(K1) in human heart failure, I(f) might favor diastolic depolarization in individual myopathic cells.
Hoppe et al. (1998) studied this question.