[The pacemaker current If: a novel pharmacological target for cardiologists]

The pacemaker current contributes to endow some types of specialized cells (either cardiomyocytes, neurons, or smooth muscle cells) with an intrinsic rhythmic activity. In cardiac cells, this current has been named If for "funny current" by DiFrancesco, who first described it more than 20 years ago. The terminology points to the most peculiar If feature: pacemaker channels activate upon membrane hyperpolarization rather than depolarization, opposite to most voltage-gated channels. Recently, electrophysiological and molecular data demonstrated that f-channels are also present in ventricular cardiomyocytes, and become upregulated in cardiac hypertrophy and failure. Misplaced expression and/or overexpression of f-channels are a consequence of electrophysiological remodeling and, from a clinical point of view, may represent an arrhythmogenic mechanism in heart failure, a condition associated with high risk for sudden cardiac death. Due to its physiological (and pathophysiological) role and to the availability of selective f-channel blockers, If can be considered as a suitable therapeutic target for cardiologists.