Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

Paul R. Coffeen, S. M.N. Efange, George C. Haidet, Scott McKnite, Rosemary B. Langason, A. B. Khare, Jennifer Pennington, Keith G Lurie

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study, We tested the utility of (+)-m-[125I]iodobenzyl)trozamicol(+)-[125I]MIBT, a novel radio ligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[125I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction system elements. Marked similarities existed between (+)-[125I]MIBT uptake and acetylcholinesterase positive regions. Optical densitometric analysis of regional (+)-[125I]MIBT uptake revealed significantly greater (+)-[125I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 ± 0.37; His bundle: 2.16 ± 0.30; right bundle branch: 0.95 ± 0.13; right atrium: 0.68 ± 0.05; right ventricle: 0.57 ± 0.03; and left ventricle: 0.57 ± 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[125I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction system elements, Thus, (+)-[125I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

Original languageEnglish (US)
Pages (from-to)923-926
Number of pages4
JournalNuclear Medicine and Biology
Volume23
Issue number7
DOIs
StatePublished - Oct 1 1996

Keywords

  • Acetylcholine
  • Autonomic nervous system
  • Cardiac conduction system
  • Receptor autoradiography
  • Vesamicol

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