Structural Identification of the Pacemaker Cells and Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels in the Heart of the Wild Atlantic Cod, Gadus morhua (Linnaeus, 1758).

Gioele Capillo,Prabhugouda Siriyappagouder,Giacomo Zaccone,Michal Kuciel,Eugenia R Lauriano,Stelios Karapanagiotis,Jose M Icardo,Jorge M O Fernandes

doi:10.3390/ijms22147539

Abstract

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 (Gadus morhua), 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.

Highlights

We have shown that the wall of the sinus venosus in G. morhua contains a complex pattern of nerves and neurons
And late studies have indicated that these nerves interact with resident intracardiac neurons, establishing a rich nervous plexus at the sinoatrial junction [5,22,26,27]
More than 90% of these neurons have been characterized as postganglionic cholinergic [5], the final rate may vary between species [27,28]

Summary

Introduction

In contrast to the contractile organs in protostomes, the morphology of the heart in deuterostomes became more complex due to the higher demands on oxygen distribution. With the exception of the Cyclostomata, the adult fish heart is formed by six chambers, or segments, arranged in the following series: sinus venosus, atrium, atrioventricular canal, ventricle, conus arteriosus, and bulbus arteriosus. Several of these chambers have acquired different morphological and functional significance across the phyletic scale (see [1]). The two main cardiac chambers, ventricle and atrium, are distinguished by the expression of chamber-specific genes, regulating their establishment and maintenance [2]

Methods

Results

Conclusion