Pacemaker channels play a major role in the generation of sinoatrial rhythmic activity. However, their expression is not confined to specialized myocardial cells, such as primary and subsidiary pacemakers. Electrophysiological and molecular data collected over the last ten years (Cerbai & Mugelli, 2006), demonstrated that f-channels are present also in non-pacemaker cardiomyocytes. These channels are highly expressed in fetal and neonatal cardiomyocytes (Cerbai et al, 1999) and even in embryonic stem (ES) cells and ES-derived cardiomyocytes (Sartiani et al, 2007). In the adult heart, I_f current densities and/or mRNA levels of its molecular correlate (i.e. hyperpolarization-activated cyclic nucleotide-gated (HCN) channels) are increased during the development of cardiac hypertrophy and failure in human and rat cardiomyocytes. Figure 1 plots the ratio between current density measured in ventricular cardiomyocytes from rat or human diseased hearts, and respective controls, bars representing confidence intervals (95%). In panel A, points represent the relative increase of I_f in rats with mild or severe left ventricular hypertrophy caused by aortic banding (Mild-LVH) or long-lasting pressure overload (Severe-LVH); in rats with overt heart failure, resulting from uncompensated hypertrophy due to pressure-overload (PO-HF) or following a myocardial infarction due to coronary ligation (PMI-HF; performed under ketamine and chlorpromazine (150 and 15 mg/kg, respectively) anaesthesia), and the relative increase of current density in patients undergoing cardiac transplantation for terminal dilated (DCM) or ischemic cardiomyopathy (ICM). Panel B shows two examples of current recorded in normal and diseased rat myocytes. For all conditions, the relative increase in I_f density was statistically significant versus controls, that is, normotensive rats, sham-operated rats, or undiseased donor hearts not transplanted for technical reasons, with the exception of DCM patients (n.s.: not significant). Over-expression of f-channels in non-pacemaker cells are one of the consequence of the process of cardiac remodeling (Cerbai et al, 1997;Cerbai et al, 1996) and it has been suggested that this phenomenon may represent an arrhythmogenic mechanism in heart failure, a condition associated with high risk for sudden cardiac death. However, it remains controversial whether I_f over-expression might play a role for the increased propensity of arrhythmias in diseased states because I_f current activation was obtained at more negative potentials in working myocardium than in pacemaker cells. The availability of selective f-channel blockers such as ivabradine may help to assess the potential arrhythmogenic function of I_f in heart disease and the role of heart rate in cardiac remodelling.