The properties of the pacemaker current I-F in human ventricular myocytes are modulated by cardiac disease

The pacemaker current I, is present in ventricular myocytes from the human failing heart where it may contribute to arrhythmogenesis. The role of card iac disease in the modulation of I, expression is still uncertain. We studi ed the functional expression and properties of I, in human ventricular myoc ytes isolated From control donor hearts or from explanted failing hearts of patients with ischemic and dilated cardiomyopathy. In patch-clamped cells, I, was elicited by hyperpolarization. Membrane capacitance (C-m) was signi ficantly higher in dilated cardiomyopathy than in control or ischemic cardi ompopathy. II was present in all ischemic and dilated cardiomyopathy tested cells and in 76% of control cells. In ischemic and dilated cardiomyopathy, I, amplitude measured at -120 mV was significantly greater than in control . However, I, density (i.e. current normalized to C-m) was significantly hi gher in ischemic cardiomyopathy (2.0+/-0.2 pA/pF) than in dilated cardiomyo pathy (1.2+/-0.1 pA/pF) or control (1.0+/-0.1 pA/pF). In diseased hearts, t he activation curve was significantly shifted to more positive values compa red to control. The slope of the fully-activated I-V relations was greater in ischemic cardiomyopathy than in dilated cardiomyopathy or control (P<0.0 5) while the intercept with the x-axis (V-rev) was similar. In conclusion, Ii is overexpressed in human ventricular myocytes From failing hearts: its functional expression seems related to the etiology of the disease, being h igher in ischemic than in dilated cardiomyopathy, and not to the degree of cell hypertrophy. (C) 2001 Academic Press.