Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand.
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 radioligand 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.
Coffeen
P R
PR
Cardiac Arrhythmia Center, University of Minnesota, Minneapolis, USA.
Efange
S M
SM
Haidet
G C
GC
McKnite
S
S
Langason
R B
RB
Khare
A B
AB
Pennington
J
J
Lurie
K G
KG
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001345:Autoradiography; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006329:Heart Conduction System / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007462:Iodobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D011950:Receptors, Cholinergic / Q000032:analysis* / Q000378:metabolism
D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D010880:Piperidines; D011950:Receptors, Cholinergic; C083232:vesamicol receptor; C081671:(3-iodobenzyl)trozamicol; D000110:Acetylcholinesterase