(Circulation. 2001;103:1638.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Acetylcholine Release in Human Heart Atrium
Influence of Muscarinic Autoreceptors, Diabetes, and Age
From Medizinische Universitätsklinik, Innere Medizin IV (V.O., E.S., T.R., L.C.R.), and Herzchirurgie (F.B.), Freiburg, Germany.
Correspondence to Lars Christian Rump, MD, Innere Medizin IV, Hugstetter Str 55, D-79106 Freiburg, Germany. E-mail lcrump{at}med1.ukl.uni-freiburg.de
Background—An
imbalance of sympathetic and parasympathetic drive to the heart is an
important risk factor for cardiac death in patients with coronary heart
disease, diabetes, and renal insufficiency. The amount of
neurotransmitter released from peripheral autonomic nerves is modulated
by presynaptic receptor systems. In analogy to 
-autoreceptors on
sympathetic nerves, muscarinic autoreceptors activated by endogenous
acetylcholine may exist on parasympathetic nerves in the human
heart.
Methods and Results—We developed a technique to study acetylcholine release from human atria and investigated muscarinic autoreceptor function. A pharmacological and molecular approach was used to characterize the subtype involved. Of the 5 muscarinic receptor subtypes cloned, only mRNA encoding for M2- and M3-receptors were detected. Potencies of several muscarinic antagonists against the release-inhibiting effect of the nonselective muscarinic agonist carbachol at the cardiac autoreceptor were correlated with published data for human cloned M1- through M5-receptors.
Conclusions—This analysis clearly indicates that acetylcholine release in human atria is controlled by muscarinic M2-receptors. Blockade of these receptors by atropine doubles the amount of acetylcholine released at a stimulation frequency of 5 Hz. In atria of patients >70 years of age and patients with late diabetic complications, acetylcholine release is reduced. Locally impaired cardiac acetylcholine release may therefore represent a pathophysiological link to sudden cardiac death in elderly and diabetic patients.
Key Words: coronary disease • nervous system, sympathetic • acetylcholine • receptors • diabetes mellitus
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