Boyett Mark R, Yanni Joseph, Tellez James, Bucchi Annalisa, Mesirca Pietro, Cai Xue, Logantha Sunil Jit R J, Wilson Claire, Anderson Cali, Ariyaratnam Jonathan, Stuart Luke, Nakao Shu, Abd Allah Eman, Jones Sandra, Lancaster Matthew, Stephenson Robert, Chandler Natalie, Smith Matthew, Bussey Carol, Monfredi Oliver, Morris Gwilym, Billeter Rudi, Mangoni Matteo E, Zhang Henggui, Hart George, D'Souza Alicia
Division of Cardiovascular Sciences, University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK.
Division of Cardiovascular Sciences, University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK.
Prog Biophys Mol Biol. 2021 Nov;166:61-85. doi: 10.1016/j.pbiomolbio.2021.06.008. Epub 2021 Jun 28.
The funny current, I, was first recorded in the heart 40 or more years ago by Dario DiFrancesco and others. Since then, we have learnt that I 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 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 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.
40多年前，达里奥·迪弗朗切斯科等人首次在心脏中记录到了滑稽电流（I）。从那时起，我们了解到I在心脏的固有起搏器——窦房结的起搏中发挥着重要作用，最近有越来越多的证据表明，I可能在动作电位通过房室（AV）结的传导中起重要作用。也有越来越多的证据表明，在正常生理条件下——运动员、昼夜节律期间、怀孕期间以及出生后发育过程中，以及病理状态下——衰老、心力衰竭、肺动脉高压、糖尿病和心房颤动，基础Hcn基因转录和翻译的调节在窦房结起搏和房室结传导的调节中起着重要作用。可能还有更多涉及Hcn基因表达变化的病理状况。在这里我们回顾I和基础HCN通道在窦房结和房室结生理及病理变化中的作用，并开始探索参与这种调节的信号通路（微小RNA、转录因子、GIRK4、自主神经系统和炎症）。这篇综述是献给退休的达里奥·迪弗朗切斯科的。
