Capillo Gioele, Lauriano Eugenia R, Icardo Jose M, Siriyappagouder Prabhugouda, Kuciel Michal, Karapanagiotis Stelios, Zaccone Giacomo, Fernandes Jorge M O
Department of Veterinary Sciences, Polo Universitario dell'Annunziata, University of Messina, 98168 Messina, Italy.
Institute of Marine Biological Resources and Biotechnology-National Research Council (IRBIM, CNR), Spianata S. Raineri, 98122 Messina, Italy.
Int J Mol Sci. 2021 Jul 14;22(14):7539. doi: 10.3390/ijms22147539.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are proteins that contain highly conserved functional domains and sequence motifs that are correlated with their unique biophysical activities, to regulate cardiac pacemaker activity and synaptic transmission. These pacemaker proteins have been studied in mammalian species, but little is known now about their heart distribution in lower vertebrates and c-AMP modulation. Here, we characterized the pacemaker system in the heart of the wild Atlantic cod (), with respect to primary pacemaker molecular markers. Special focus is given to the structural, ultrastructural and molecular characterization of the pacemaker domain, through the expression of HCN channel genes and the immunohistochemistry of HCN isoforms, including the location of intracardiac neurons that are adjacent to the sinoatrial region of the heart. Similarly to zebrafish and mammals, these neurons are immunoreactive to ChAT, VAChT and nNOS. It has been shown that cardiac pacemaking can be modulated by sympathetic and parasympathetic pathways, and the existence of intracardiac neurons projecting back to the central nervous system provide a plausible link between them.
超极化激活的环核苷酸门控（HCN）通道是一类蛋白质，其包含与独特生物物理活性相关的高度保守的功能域和序列基序，用于调节心脏起搏器活动和突触传递。这些起搏器蛋白已在哺乳动物物种中得到研究，但目前对于它们在低等脊椎动物心脏中的分布以及c - AMP调节知之甚少。在此，我们针对主要的起搏器分子标记物，对野生大西洋鳕鱼心脏中的起搏器系统进行了表征。通过HCN通道基因的表达以及HCN亚型的免疫组织化学，特别关注起搏器区域的结构、超微结构和分子特征，包括与心脏窦房区域相邻的心内神经元的位置。与斑马鱼和哺乳动物类似，这些神经元对ChAT、VAChT和nNOS具有免疫反应性。研究表明，心脏起搏可通过交感和副交感神经通路进行调节，而投射回中枢神经系统的心内神经元的存在为它们之间提供了一个合理的联系。
