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

Y1 - 2013

N2 - INTRODUCTION: 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 (IK,ACh). The effect of ACh in ventricle is still debated. We compare the effect of ACh on action potentials in canine atria, Purkinje and ventricular tissue as well as on ionic currents in isolated cells. METHODS: 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. RESULTS: In atrial tissue, ACh hyperpolarized the membrane potential and shortened 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 ICa was observed in atria, Endo and Epi after ACh. ICa inhibition increased at faster pacing rates. At a BCL of 400 ms, ACh (1 µM) reduced ICa to 68% of control. CONCLUSION: IK,ACh is highly expressed in atria and is negligible/absent in Purkinje, Endo and Epi. In all cardiac tissues ACh caused rate-dependent inhibition of ICa.

AB - INTRODUCTION: 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 (IK,ACh). The effect of ACh in ventricle is still debated. We compare the effect of ACh on action potentials in canine atria, Purkinje and ventricular tissue as well as on ionic currents in isolated cells. METHODS: 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. RESULTS: In atrial tissue, ACh hyperpolarized the membrane potential and shortened 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 ICa was observed in atria, Endo and Epi after ACh. ICa inhibition increased at faster pacing rates. At a BCL of 400 ms, ACh (1 µM) reduced ICa to 68% of control. CONCLUSION: IK,ACh is highly expressed in atria and is negligible/absent in Purkinje, Endo and Epi. 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

VL - 305

SP - H66-H75

JO - A J P: Heart and Circulatory Physiology (Online)

JF - A J P: Heart and Circulatory Physiology (Online)

SN - 1522-1539

ER -