Acetylcholine release in human heart atrium: influence of muscarinic autoreceptors, diabetes, and age.

Abstract:

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 alpha-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 M(2)- and M(3)-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 M(1)- through M(5)-receptors. CONCLUSIONS:This analysis clearly indicates that acetylcholine release in human atria is controlled by muscarinic M(2)-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.

journal_name

Circulation

journal_title

Circulation

authors

Oberhauser V,Schwertfeger E,Rutz T,Beyersdorf F,Rump LC

doi

10.1161/01.cir.103.12.1638

subject

Has Abstract

pub_date

2001-03-27 00:00:00

pages

1638-43

issue

12

eissn

0009-7322

issn

1524-4539

journal_volume

103

pub_type

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