title: Distribution and morphology of calcitonin gene-related peptide and substance P immunoreactive axons in the whole-mount atria of mice.
abstract: The murine model has been used to investigate the role of cardiac sensory axons in various disease states. However, the distribution and morphological structures of cardiac nociceptive axons in normal murine tissues have not yet been well characterized. In this study, whole-mount atria from FVB mice were processed with calcitonin gene-related peptide (CGRP) and substance P (SP) primary antibodies followed by secondary antibodies, and then examined using confocal microscopy. We found: 1) Large CGRP-IR axon bundles entered the atria with the major veins, and these large bundles bifurcated into small bundles and single axons that formed terminal end-nets and free endings in the epicardium. Varicose CGRP-IR axons had close contacts with muscle fibers, and some CGRP-IR axons formed varicosities around principle neurons (PNs) within intrinsic cardiac ganglia (ICGs). 2) SP-IR axons also were found in the same regions of the atria, attached to veins, and within cardiac ganglia. Similar to CGRP-IR axons, these SP-IR axons formed terminal end-nets and free endings in the atrial epicardium and myocardium. Within ICGs, SP-IR axons formed varicose endings around PNs. However, SP-IR nerve fibers were less abundant than CGRP-IR fibers in the atria. 3) None of the PNs were CGRP-IR or SP-IR. 4) CGRP-IR and SP-IR often colocalized in terminal varicosities around PNs. Collectively, our data document the distribution pattern and morphology of CGRP-IR and SP-IR axons and terminals in different regions of the atria. This knowledge provides useful information for CGRP-IR and SP-IR axons that can be referred to in future studies of pathological remodeling.
authors.affiliation: Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, United States.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Hatcher
authors.affiliation: Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Donald B
authors.initials: DB
authors.lastname: Hoover
authors.affiliation: Department of Anesthesia, University of Iowa Hospital and Clinics, Iowa City, IA 52242, United States.
authors.forename: He
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Physiology, Loyola University, Stritch School of Medicine, Maywood, IL 60153, United States.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Wurster
authors.affiliation: Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, United States. Electronic address: zcheng@mail.ucf.edu.
authors.forename: Zixi Jack
authors.initials: ZJ
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D006321:Heart / Q000033:anatomy & histology* / Q000294:innervation*; D006325:Heart Atria / Q000033:anatomy & histology / Q000294:innervation; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000033:anatomy & histology / Q000294:innervation; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000033:anatomy & histology / Q000378:metabolism; D010496:Pericardium / Q000033:anatomy & histology / Q000294:innervation; D017729:Presynaptic Terminals / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D014680:Veins / Q000033:anatomy & histology
chemical_list: D013373:Substance P; D015740:Calcitonin Gene-Related Peptide
keywords: Atria; CGRP; Cardiac ganglia; Neuropeptides; Nociceptive; SP