Abstract
The mouse heart is a popular model to study the function and autonomic control of
the specialized cardiac conduction system (CCS). However, the precise identity and
anatomical distribution of the intrinsic cardiac nerves that modulate the function
of the mouse CCS have not been adequately studied. We aimed at determining the organization
and distribution of the intrinsic cardiac nerves that supply the CCS of the mouse.
In whole mouse heart preparations, intrinsic neural structures were revealed by histochemical
staining for acetylcholinesterase (AChE). Adrenergic, cholinergic and peptidergic
neural components were identified, respectively, by immunohistochemical labeling for
tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), calcitonin gene related
peptide (CGRP), substance P (SP), and protein gene product 9.5 (PGP 9.5). Myocytes
of the CCS were identified by immunolabeling of hyperpolarization activated cyclic
nucleotide-gated potassium channel 4 (HCN4). In addition, the presence of CCS myocytes
in atypical locations was verified using fluorescent immunohistochemistry performed
on routine paraffin sections. The results demonstrate that four microscopic epicardial
nerves orientated toward the sinuatrial nodal (SAN) region derive from both the dorsal
right atrial and right ventral nerve subplexuses. The atrioventricular nodal (AVN)
region is typically supplied by a single intrinsic nerve derived from the left dorsal
nerve subplexus at the posterior interatrial groove. SAN myocytes positive for HCN4
were widely distributed both on the medial, anterior, lateral and even posterior sides
of the root of the right cranial (superior caval) vein. The distribution of HCN4-positive
myocytes in the AVN region was also wider than previously considered. HCN4-positive
cells and thin slivers of the AVN extended to the roots of the ascending aorta, posteriorly
to the orifice of the coronary sinus, and even along both atrioventricular rings.
Notwithstanding the fact that cholinergic nerve fibers and axons clearly predominate
in the mouse CCS, adrenergic nerve fibers and axons are abundant therein as well.
Altogether, these results provide new insight into the anatomical basis of the neural
control of the mouse CCS.
Keywords
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References
- Developmental origin, growth, and three-dimensional architecture of the atrioventricular conduction axis of the mouse heart.Circ. Res. 2010; 107: 728-736
- The disposition and innervation of atrioventricular ring specialized tissue in rats and rabbits.J. Anat. 1972; 113: 197-211
- The disposition, morphology and innervation of cardiac specialized tissue in the guinea-pig.J. Anat. 1972; 111: 453-468
- The anatomy of the cardiac conduction system.Clin. Anat. 2009; 22: 99-113
- Electrophysiology of single heart cells from the rabbit tricuspid valve.J. Physiol. 1990; 425: 145-167
- Physiology and pharmacology of the cardiac pacemaker (“funny”) current.Pharmacol. Ther. 2005; 107: 59-79
- Topographic morphology and age-related analysis of the neuronal number of the rat intracardiac nerve plexus.Ann. Anat. 2003; 185: 449-459
- Architecture and age-related analysis of the neuronal number of the guinea pig intrinsic cardiac nerve plexus.Ann. Anat. 2005; 187: 225-243
- Spatiotemporal electrophysiological changes in a murine ablation model.Europace. 2011; 13: 1494-1500
- Whole-mount demonstration of cholinesterase-containing nerves in the right atrial wall, nodal tissue, and atrioventricular bundle of the pig heart.J. Anat. 1971; 108: 375-386
- Rabbit heart nodal tissue, sinuatrial ring bundle and atrioventricular connexions indentified as a neuromuscular system.J. Anat. 1972; 112: 367-382
- The sinoatrial node, a heterogeneous pacemaker structure.Cardiovasc. Res. 2000; 47: 658-687
- Autonomic innervation of the human cardiac conduction system: changes from infancy to senility—an immunohistochemical and histochemical analysis.Anat. Rec. 2001; 264: 169-182
- Innervation of the human cardiac conduction system. A quantitative immunohistochemical and histochemical study.Circulation. 1994; 89: 1697-1708
- A quantitative assessment of innervation in the conduction system of the calf heart.Anat. Rec. 1996; 245: 685-698
- A quantitative study of nerve distribution in the conduction system of the guinea pig heart.J. Anat. 1996; 188: 403-416
- Localisation and quantitation of autonomic innervation in the porcine heart I: conduction system.J. Anat. 1999; 195: 341-357
- Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy.Microvasc. Res. 2006; 72: 20-26
- Functional anatomy of the murine sinus node: high-resolution optical mapping of ankyrin-B heterozygous mice.Am. J. Physiol. Heart Circ. Physiol. 2010; 299: H482-H491
- The sino-atrial node of the rat heart.Anat. Rec. 1955; 123: 425-435
- The dual blood supply of the rat heart.Am. J. Anat. 1957; 101: 1-16
- Localization of cholinergic innervation in guinea pig heart by immunohistochemistry for high-affinity choline transporters.Cardiovasc. Res. 2004; 62: 112-121
- Cholinergic innervation of the canine and human ventricular conducting system. Anatomic and electrophysiologic correlations.Circulation. 1974; 50: 948-955
- Role of Pyk2 in cardiac arrhythmogenesis.Am. J. Physiol. Heart Circ. Physiol. 2011; 301: H975-H983
- Organisation of the mouse sinoatrial node: structure and expression of HCN channels.Cardiovasc. Res. 2007; 73: 729-738
- Atrioventricular junctional tissue. Discrepancy between histological and electrophysiological characteristics.Circulation. 1996; 94: 571-577
- Immunohistochemical delineation of the conduction system. I: The sinoatrial node.Cardiovasc. Res. 1993; 73: 473-481
- Anatomical study of the neural ganglionated plexus in the canine right atrium: implications for selective denervation and electrophysiology of the sinoatrial node in dog.Anat. Rec. 1999; 255: 271-294
- Morphology, distribution, and variability of the epicardiac neural ganglionated subplexuses in the human heart.Anat. Rec. 2000; 259: 353-382
- Morphology of the intrinsic cardiac nervous system in the dog: a whole-mount study employing histochemical staining with acetylcholinesterase.Cells Tissues Organs. 2002; 172: 297-320
- Spatial distribution of nerve processes and beta-adrenoreceptors in the rat atrioventricular node.J. Anat. 1998; 192: 517-528
- Morphological study of the innervation pattern of the rabbit sinoatrial node.Am. J. Anat. 1989; 185: 74-88
- Iron overload decreases CaV1.3-dependent L-type Ca2+ currents leading to bradycardia, altered electrical conduction, and atrial fibrillation.Circulation. 2011; 4: 733-742
- Automaticity in atrioventricular valve leaflets of rabbit heart.Am. J. Physiol. 1986; 250: H397-H406
- Morphologic pattern of the intrinsic ganglionated nerve plexus in mouse heart.Heart Rhythm. 2011; 8: 448-454
- Immunohistochemical characterization of the intrinsic cardiac neural plexus in whole-mount mouse heart preparations.Heart Rhythm. 2011; 8: 731-738
- Location and variability of epicardiac ganglia in human fetuses.Anat. Embryol. (Berl). 2006; 6: 585-594
- The epicardial neural ganglionated plexus of the ovine heart: anatomical basis for experimental cardiac electrophysiology and nerve protective cardiac surgery.Heart Rhythm. 2010; 7: 942-950
- Differential chronotropic and dromotropic responses to focal stimulation of cardiac vagal ganglia in the rat.Exp. Physiol. 2003; 88: 315-327
- Distribution of atrial and nodal cells within the rabbit sinoatrial node: models of sinoatrial transition.Circulation. 1998; 97: 1623-1631
- Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution.Cardiovasc. Res. 2001; 52: 40-50
- Extended atrial conduction system characterised by the expression of the HCN4 channel and connexin45.Cardiovasc. Res. 2006; 72: 271-281
- The extent of the specialized atrioventricular ring tissues.Heart Rhythm. 2009; 6: 672-680
Article info
Publication history
Published online: February 11, 2013
Accepted:
January 8,
2013
Received in revised form:
January 7,
2013
Received:
November 14,
2012
Identification
Copyright
© 2013 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
