TY - JOUR
T1 - Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand
AU - Coffeen, Paul R.
AU - Efange, S. M.N.
AU - Haidet, George C.
AU - McKnite, Scott
AU - Langason, Rosemary B.
AU - Khare, A. B.
AU - Pennington, Jennifer
AU - Lurie, Keith G.
N1 - Funding Information:
This work was supportedb y theA mericanH eart Association,M innesota Affiliate, Grant-in Aid. Part of thisw ork was presented in abstract fom at theN orth American Society of Pacinga nd Elecnophysiologmy eeting, May 1993. The authorst hankB arry Detlofff or his technicaal ssistance.
PY - 1996/10
Y1 - 1996/10
N2 - 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.
AB - 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.
KW - Acetylcholine
KW - Autonomic nervous system
KW - Cardiac conduction system
KW - Receptor autoradiography
KW - Vesamicol
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U2 - 10.1016/S0969-8051(96)00132-1
DO - 10.1016/S0969-8051(96)00132-1
M3 - Article
C2 - 8971861
AN - SCOPUS:0030271671
VL - 23
SP - 923
EP - 926
JO - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
SN - 0969-8051
IS - 7
ER -
