Different expression of the pacemaker current If in human ventricular myocytes from ischemic and dilated failing heart.

Recent demonstration of the presence of the pacemaker current If in ventricular myocytes (HuVM) isolated from the human failing heart suggests that it may contribute to arrhythmias in this setting. It is uncertain if the expression of If in HuVM is increased in diseased with respect to undiseased hearts. To address this point, we compared If occurrence and properties in HuVM isolated from control donor hearts (CTR, n=3) or from explanted failing hearts of patients with ischemic (ICM, n=9) and dilated (DCM, n=9) cardiomyopathy. Patch-clamped cells were superfused with a modified Tyrode solution also containing (mM): KCl 25, BaCl2 2, MnCl2 2, 4-aminopyridine 0.5. If was elicited by hyperpolarization (range: -60 to -140 mV); Boltzmann fitting of the activation curve was used to measure midpoint (VH) and maximum specific conductance (gmax). Membrane capacitance (Cm), and index of cell size and hypertrophy, was significantly higher in DCM (mean±sem: 333±24 pF, n=49) than in CTR (212±18 pF, n=44) or ICM (272±24 pF, n=39). If was present in all ICM and DCM tested cells and in 75% of CTR cells. In ICM cells, If amplitude measured at -120 mV was significantly greater than in CTR (424±44 pA vs. 237±34 pA, p<0.05) and similar to DCM (380±34 pA) HuVM; however, If density, i.e. current normalized to Cm, was significantly higher in ICM (1.8±0.2 pA/pF) than in either DCM (1.2±0.1 pA/pF, n=49) or CTR HuVM (1.1±0.1 pA/pF, n=23) (p<0.05). Also gmax was significantly higher in ICM (22.5±5.2 pS/pF) than in CTR (10.7±1.3 pS/pF) and DCM HuVM (11.2±0.9 pS/pF) (p<0.05), while VH was not different in the 3 groups (ICM, -71±2 mV; DCM, -74±1 mV; CTR, -78±2 mV). Thus If is over-expressed in HuVM from failing hearts; its expression seems related to the etiology of the disease (ICM>DCM) and not to the degree of cell hypertrophy.