Discovered some 40 years ago, the I_f current has since been known as the “pacemaker” current due to its role in the initiation and modulation of the heartbeat and of neuronal excitability. But this is not all, the funny current keeps entertaining the researchers; indeed, several data discovering novel and uncanonical roles of f/HCN channel are quickly accumulating. In the present review, we provide an overview of the expression and cellular functions of HCN/f channels in a variety of systems/organs, and particularly in sour taste transduction, hormones secretion, activation of astrocytes and microglia, inhibition of osteoclastogenesis, renal ammonium excretion, and peristalsis in the gastrointestinal and urine systems. We also analyzed the role of HCN channels in sustaining cellular respiration in mitochondria and their participation to mitophagy under specific conditions. The relevance of HCN currents in undifferentiated cells, and specifically in the control of stem cell cycle and in bioelectrical signals driving left/right asymmetry during zygote development, is also considered. Finally, we present novel data concerning the expression of HCN mRNA in human leukocytes.

We can thus conclude that the emerging evidence presented in this review clearly points to an increasing interest and importance of the “funny” current that goes beyond its role in cardiac sinoatrial and neuronal excitability regulation.

大约 40 年前发现的 I _f电流因其在心跳和神经元兴奋性的启动和调节中的作用而被称为“起搏器”电流。但这还不是全部，有趣的潮流一直在逗乐研究人员；事实上，一些发现 f/HCN 通道的新颖和非规范作用的数据正在迅速积累。在本综述中，我们概述了 HCN/f 通道在各种系统/器官中的表达和细胞功能，特别是在酸味转导、激素分泌、星形胶质细胞和小胶质细胞的激活、破骨细胞生成的抑制、肾氨胃肠道和尿液系统中的排泄和蠕动。我们还分析了 HCN 通道在维持线粒体细胞呼吸中的作用以及它们在特定条件下对线粒体自噬的参与。还考虑了 HCN 电流在未分化细胞中的相关性，特别是在控制干细胞周期和在受精卵发育过程中驱动左右不对称的生物电信号中的相关性。最后，我们提出了关于人类白细胞中 HCN mRNA 表达的新数据。

因此，我们可以得出结论，本综述中提出的新证据清楚地表明“有趣”电流的兴趣和重要性日益增加，超出了其在心脏窦房和神经元兴奋性调节中的作用。