The Properties of the Pacemaker Current IFin Human Ventricular Myocytes are Modulated by Cardiac Disease

The pacemaker current Ifis present in ventricular myocytes from the human failing heart where it may contribute to arrhythmogenesis. The role of cardiac disease in the modulation of Ifexpression is still uncertain. We studied the functional expression and properties of Ifin human ventricular myocytes isolated from control donor hearts or from explanted failing hearts of patients with ischemic and dilated cardiomyopathy. In patch-clamped cells, Ifwas elicited by hyperpolarization. Membrane capacitance (Cm) was significantly higher in dilated cardiomyopathy than in control or ischemic cardiomyopathy. Ifwas present in all ischemic and dilated cardiomyopathy tested cells and in 76% of control cells. In ischemic and dilated cardiomyopathy, Ifamplitude measured at −120 mV was significantly greater than in control. However, Ifdensity (i.e. current normalized to Cm) was significantly higher in ischemic cardiomyopathy (2.0±0.2 pA/pF) than in dilated cardiomyopathy (1.2±0.1 pA/pF) or control (1.0±0.1 pA/pF). In diseased hearts, the activation curve was significantly shifted to more positive values compared to control. The slope of the fully-activated I–V relations was greater in ischemic cardiomyopathy than in dilated cardiomyopathy or control (P<0.05) while the intercept with the x -axis (Vrev) was similar. In conclusion, Ifis overexpressed in human ventricular myocytes from failing hearts; its functional expression seems related to the etiology of the disease, being higher in ischemic than in dilated cardiomyopathy, and not to the degree of cell hypertrophy.