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Toxicologic Pathology
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The Monkey (Macaca fascicularis) Heart Neural Structures and Conducting System: An Immunochemical Study of Selected Neural Biomarkers and Glutamate Receptors

Ruedi W. Mueller

Banting Research Center, Tunney's Pasture, Health Canada, Ottawa, Ontario, Canada K1A 0L2

Santokh S. Gill

Banting Research Center, Tunney's Pasture, Health Canada, Ottawa, Ontario, Canada K1A 0L2, santokh_gill{at}hs-sc.gc.ca

Olga M. Pulido

Banting Research Center, Tunney's Pasture, Health Canada, Ottawa, Ontario, Canada K1A 0L2

The neural markers, protein gene product 9.5 (PGP 9.5), neurofilaments (NF) and glutamate receptors (GluRs) were visualized by immunohistochemistry in the monkey heart. PGP 9.5 showed the greatest affinity for intramural ganglia cells and nerve fibres. Structural components of the conducting system were also stained, particularly the bundle of His, AV node and Purkinje fibres. Anti-NF 200 and NF 160 showed strong, preferential affinity to nerve fibres and ganglia throughout the heart. Further studies concentrated on the presence and the distribution of glutamate receptors: NMDAR 1, GluR 1, GluR 2/3, GluR 5/6/7, mGluR 2/3, and mGluR 5. Positive immunoreactivity of GluRs was evident in nerve terminals within the atrium, myocardium, intramural ganglia and elements of the conducting system. The intensity of the stain varied for each antibody according to the anatomical distribution within neural structures and conducting system. The specificity of immunolabelling was confirmed by absorption studies with each corresponding peptide. There is preferential affinity to and differential distribution of staining with PGP 9.5, NFs and several subtypes of GluRs in the various components of the cardiac conducting system in adult monkeys. The expression of specific neural markers and glutamate receptors common to nerve fibers and ganglia cells is consistent to our previous report in rodents. These expressions suggests that such structures in the heart share common characteristics with a variety of neural tissues and hence are potential targets for neurotoxins. Furthermore, the strong affinity and specific distribution of several subtypes of GluRs in the monkey heart fosters our view that these receptors may be able to influence the physiology and pathophysiology of cardiac rhythm and excitation. Hence as in the brain, the GluRs may be involved in the mediation of excitatory effects in the heart.

Key Words: Glutamate receptors • cardiotoxicity • immunohistochemistry • monkey.

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Toxicologic Pathology, Vol. 31, No. 2, 227-234 (2003)
DOI: 10.1080/01926230390183724
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