MEASUREMENT OF FUNCTIONAL CHOLINERGIC INNERVATION IN RAT-HEART WITH ANOVEL VESAMICOL RECEPTOR-LIGAND

Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of +)-m-[I -125]iodobenzyl)trozamicol(+)-[I-125]MIBT), a novel radioligand ligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of choliner gic activity in the conduction system. The (+)-[I-125]MIBT was injecte d intravenously into four rats. Three hours later, the rats were kille d and their hearts were frozen. Quantitative autoradiography was perfo rmed on 20-micron-thick sections that were subsequently stained for ac etylcholinesterase to identify specific conduction system elements. Ma rked similarities existed between (+)-[I-125]MIBT uptake and acetylcho linesterase positive regions. Optical densitometric analysis of region al (+)-[I-125]MIBT uptake revealed significantly greater (+)-[I-125]MI BT 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; an d left ventricle: 0.57 +/- 0.03; p < 0.05 comparing conduction element s with ventricular muscle). This study demonstrates that (+) [I-125]MI BT binds avidly to cholinergic nerve tissue innervating specific condu ction system elements. Thus, (+)-[I-125]MIBT may be a useful functiona l marker in studies on cholinergic innervation in the cardiac conducti on system. Copyright (C) 1996 Elsevier Science Inc.