Kodirov Sodikdjon A
Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg, Russia; Institute of Physiology and Pathophysiology, University of Mainz, Germany; University of Texas at Brownsville, Department of Biological Sciences, TX 78520, USA; Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal; Institute of Biophysics, Johannes Kepler University, Linz, Austria.
Comp Biochem Physiol C Toxicol Pharmacol. 2025 Sep;295:110205. doi: 10.1016/j.cbpc.2025.110205. Epub 2025 Apr 14.
To some extent, the main role of hyperpolarization-activated cyclic nucleotide-gated non-selective cation channels (HCN, I, or I), pace-making, is dogmatized as a functional expression of one or another alpha subunit of HCN channels does not make every region of the brain or heart a pacemaker one. Recent research hints at the role of HCN in arrhythmias and seizures that are often caused by voltage-dependent K and Na channels (Kv and Nav) and neurotransmitters, respectively. There are many parallels between the HCN and K channels. Similar to Kv channels, an altered HCN function also leads to long QT interval. Moreover, a mutation in HCN is believed to trigger correlated arrhythmias and, e.g., epilepsy, among many other brain pathologies. Unlike Kv channels, although no dedicated ancillary beta subunit has been discovered for HCN, the I properties are also influenced by other elements and factors. A new interaction has been discovered between HCN and the vesicle-associated membrane protein (VAMP). The prevailing interaction occurs via the subtype VAMP-associated protein B (VAPB). However, this interaction is not unique but universal, since there is also a link between Kv2.1 and VAMP2 (vesicular SNARE). The most remarkable similitude is the fact that a selective antagonist of HCN and medication ivabradine prevents the I via the cloned human ether-à-go-go-related gene (HERG) channels, also known as KvLQT and Kv11.1 alpha subunit.
在一定程度上，超极化激活的环核苷酸门控非选择性阳离子通道（HCN通道，即I f或I h通道）的主要功能——起搏作用，被教条化了，因为HCN通道某个α亚基的功能性表达并不会使大脑或心脏的每个区域都成为起搏点。最近的研究暗示了HCN通道在心律失常和癫痫发作中的作用，心律失常和癫痫发作通常分别由电压依赖性钾通道和钠通道（Kv和Nav）以及神经递质引起。HCN通道和钾通道之间存在许多相似之处。与Kv通道类似，HCN通道功能改变也会导致QT间期延长。此外，人们认为HCN通道的突变会引发相关的心律失常，例如癫痫以及许多其他脑部疾病。与Kv通道不同，尽管尚未发现HCN通道有专门的辅助β亚基，但其I f特性也受其他元件和因素的影响。人们发现HCN通道与囊泡相关膜蛋白（VAMP）之间存在一种新的相互作用。这种主要的相互作用是通过VAMP相关蛋白B亚型（VAPB）发生的。然而，这种相互作用并非HCN通道所独有，而是普遍存在的，因为Kv2.1通道与VAMP2（囊泡SNARE）之间也存在联系。最显著的相似之处在于，HCN通道的选择性拮抗剂和药物伊伐布雷定可通过克隆的人类ether-à-go-go相关基因（HERG）通道（也称为KvLQT和Kv11.1α亚基）来抑制I f电流。
