The funny current, I_f, was first recorded in the heart 40 or more years ago by Dario DiFrancesco and others. Since then, we have learnt that I_f plays an important role in pacemaking in the sinus node, the innate pacemaker of the heart, and more recently evidence has accumulated to show that I_f may play an important role in action potential conduction through the atrioventricular (AV) node. Evidence has also accumulated to show that regulation of the transcription and translation of the underlying Hcn genes plays an important role in the regulation of sinus node pacemaking and AV node conduction under normal physiological conditions - in athletes, during the circadian rhythm, in pregnancy, and during postnatal development - as well as pathological states - ageing, heart failure, pulmonary hypertension, diabetes and atrial fibrillation. There may be yet more pathological conditions involving changes in the expression of the Hcn genes. Here, we review the role of I_f and the underlying HCN channels in physiological and pathological changes of the sinus and AV nodes and we begin to explore the signalling pathways (microRNAs, transcription factors, GIRK4, the autonomic nervous system and inflammation) involved in this regulation. This review is dedicated to Dario DiFrancesco on his retirement.

有趣的电流I _f是 40 多年前由 Dario DiFrancesco 和其他人首次记录在心脏中的。从那时起，我们了解到I _f在窦房结（心脏的先天起搏器）的起搏中起重要作用，并且最近积累的证据表明I _f可能在通过房室传导的动作电位中起重要作用(AV) 节点。越来越多的证据表明，对潜在Hcn转录和翻译的调控基因在正常生理条件下（运动员、昼夜节律期间、怀孕期间和产后发育期间）以及病理状态（衰老、心力衰竭、肺动脉高压）下的窦房结起搏和房室结传导的调节中起重要作用、糖尿病和心房颤动。可能还有更多的病理状况涉及Hcn基因表达的变化。在这里，我们回顾一下I _f的作用以及潜在的 HCN 通道在窦房结和 AV 结的生理和病理变化中的作用，我们开始探索参与该调节的信号通路（microRNAs、转录因子、GIRK4、自主神经系统和炎症）。这篇评论是献给达里奥·迪弗朗西斯科（Dario DiFrancesco）退休的。