Progress in Biophysics and Molecular Biology ( IF 3.8 ) Pub Date : 2021-07-06 , DOI: 10.1016/j.pbiomolbio.2021.06.010 Joanna Xia 1 , Eric A Accili 1
The funny current, and the HCN channels that form it, are affected by the direct binding of cyclic nucleotides. Binding of these second messengers causes a depolarizing shift of the activation curve, which leads to greater availability of current at physiological membrane voltages. This review outlines a brief history on this regulation and provides some evidence that other cyclic nucleotides, especially cGMP, may be important for the regulation of the funny channel in the heart. Current understanding of the molecular mechanism of cyclic nucleotide regulation is also presented, which includes the notions that full and partial agonism occur as a consequence of negatively cooperative binding. Knowledge gaps, including a potential role of cyclic nucleotide-regulation of the funny current under pathophysiological conditions, are included. The work highlighted here is in dedication to Dario DiFrancesco on his retirement.
中文翻译:
环核苷酸对窦房有趣通道的调节:从肾上腺素和 IK2 到配体与蛋白质亚基的直接结合
有趣的电流和形成它的 HCN 通道受到环核苷酸直接结合的影响。这些第二信使的结合导致激活曲线的去极化移动,这导致在生理膜电压下电流的可用性更大。这篇综述概述了该调节的简要历史,并提供了一些证据表明其他环核苷酸,尤其是 cGMP,可能对调节心脏中的有趣通道很重要。还介绍了目前对环核苷酸调节的分子机制的理解,其中包括由于负协同结合而发生完全和部分激动的概念。知识差距,包括在病理生理条件下循环核苷酸调节有趣电流的潜在作用。