title: Tissue-specific effects of acetylcholine in the canine heart.
abstract: Acetylcholine (ACh) release from the vagus nerve slows heart rate and atrioventricular conduction. ACh stimulates a variety of receptors and channels, including an inward rectifying current [ACh-dependent K⁺ current (IK,ACh)]. The effect of ACh in the ventricle is still debated. We compared the effect of ACh on action potentials in canine atria, Purkinje, and ventricular tissue as well as on ionic currents in isolated cells. Action potentials were recorded from ventricular slices, Purkinje fibers, and arterially perfused atrial preparations. Whole cell currents were recorded under voltage-clamp conditions, and unloaded cell shortening was determined on isolated cells. The effect of ACh (1-10 μM) as well as ACh plus tertiapin, an IK,ACh-specific toxin, was tested. In atrial tissue, ACh hyperpolarized the membrane potential and shortened the action potential duration (APD). In Purkinje and ventricular tissues, no significant effect of ACh was observed. Addition of ACh to atrial cells activated a large inward rectifying current (from -3.5 ± 0.7 to -23.7 ± 4.7 pA/pF) that was abolished by tertiapin. This current was not observed in other cell types. A small inhibition of Ca²⁺ current (ICa) was observed in the atria, endocardium, and epicardium after ACh. ICa inhibition increased at faster pacing rates. At a basic cycle length of 400 ms, ACh (1 μM) reduced ICa to 68% of control. In conclusion, IK,ACh is highly expressed in atria and is negligible/absent in Purkinje, endocardial, and epicardial cells. In all cardiac tissues, ACh caused rate-dependent inhibition of ICa.
authors: Department of Veterinary Clinical and Animal Science, University of Copenhagen, Frederiksberg, Denmark. kirstine@callo.dk
authors: Kirstine
authors: K
authors: Calloe
authors: Robert
authors: R
authors: Goodrow
authors: Søren-Peter
authors: SP
authors: Olesen
authors: Charles
authors: C
authors: Antzelevitch
authors: Jonathan M
authors: JM
authors: Cordeiro
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004285:Dogs; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology; D009928:Organ Specificity; D011188:Potassium / Q000378:metabolism
chemical_list: D000109:Acetylcholine; D011188:Potassium
keywords: Purkinje fiber; acetylcholine; atria; ionic currents; ventricle
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