TY - JOUR
T1 - Tissue-specific effects of acetylcholine in the canine heart
AU - Callø, Kirstine
AU - Goodrow, Robert
AU - Olesen, Søren-Peter
AU - Antzelevitch, Charles
AU - Cordeiro, Jonathan M.
PY - 2013/7/1
Y1 - 2013/7/1
N2 - 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
AB - 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
U2 - 10.1152/ajpheart.00029.2013
DO - 10.1152/ajpheart.00029.2013
M3 - Journal article
C2 - 23645460
SN - 1522-1539
VL - 305
SP - H66-H75
JO - A J P: Heart and Circulatory Physiology (Online)
JF - A J P: Heart and Circulatory Physiology (Online)
ER -