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(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

Vitus Oberhauser, PhD; Eckhard Schwertfeger, MD; Tobias Rutz; Friedhelm Beyersdorf, MD; Lars Christian Rump, MD

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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