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ACh Synaptic Accumulation leads to Increased, Atrioventricular block and bradycardia
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
In cardiac tissue, acetylcholine acts on M2 type muscarinic receptors. M2 receptors tend to mediate inhibition of cellular activity through activation of G proteins that inhibit adenylyl cyclase and activation of potassium channels in the plasma membrane. Activation of potassium channels by the M2 receptors alters the electrophysiology of supraventricular cells leading to arrhythmias (such as atrioventricular blockade) and decreased heart rate (bradycardia).
Evidence Collection Strategy
Evidence Supporting this KER
Given the role of acetylcholine in regulating heart rate, it is highly plausible that accumulation of acetylcholine in the synapses associated with cardiac tissue would lead to arrhythmias and decreased heart rate.
Uncertainties and Inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Available data suggests this relationship is relevant to all organisms with heart tissue.
- Dexter F, Saidel GM, Levy MN, Rudy Y. 1989. Mathematical model of dependence of heart rate on tissue concentration of acetylcholine. American J. Physiol. - Heart and Circulatory Physiology. 256: H520-H526.
- Hsieh DJ, Liao CF. 2002. Zebrafish M2 muscarinic acetylcholine receptor: cloning, pharmacological characterization, expression patterns and roles in embryonic bradycardia.
- Golan, David E (editor). “Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy”, 2nd edition. LWW: 2008.
- Katzung, B. “Basic & Clinical Pharmacology”, 10th Edition. Mc Graw Hill Medical: 2007
- Harvey, Richard; Champe, Pamela (series editors). “Lippincott illustrated reviews: Pharmacology”, 4th edition. LWW: 2009