© 1995 by European Society of Cardiology
Copyright © 1995, European Society of Cardiology
Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node
aDepartment of Circulation and Respiration, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
bDepartment of Physiology, University of Leeds, Leeds LS2 9JT, United Kingdom
* Correspondence to Dr Boyett.
Objective: The aim was to study the ionic basis of the chronotropic effects of bath applied acetylcholine and vagal stimulation on the rabbit sinoatrial node. Methods: The chronotropic effect of bath applied acetylcholine was measured in single cells and small multicellular preparations from the rabbit sinoatrial node and the chronotropic effect of postganglionic vagal stimulation was measured in the intact sinoatrial node. The roles of the hyperpolarisation activated current, if, the acetylcholine activated potassium current, iK,ACh, and the L-type calcium current, iCa, were investigated by blocking the currents with 1–2 mM Cs+ or 10–6 M UL-FS49, 0.2–1.0 mM Ba2+, and 6 x 10–6 M nifedipine, respectively. Results: Under control conditions, small multicellular preparations were approximately two orders of magnitude less sensitive to bath applied acetylcholine than single cells. However, after block of acetylcholinesterase by eserine in small multicellular preparations the sensitivities of the two types of preparation were approximately the same. Block of if either had no discernible effect or increased the chronotropic effect of bath applied acetylcholine on single cells or small multicellular preparations, whereas partial block of iK,ACh reduced it substantially. Similarly, block of if did not suppress the initial slowing of spontaneous action potentials by vagal stimulation, whereas partial block of iK,ACh reduced it. The hyperpolarisation of the arrested sinoatrial node in response to vagal stimulation was also substantially reduced by block of iK,ACh. Partial block of iCa caused large decreases in the action potential amplitude and maximum diastolic potential, but little decrease in the rate of spontaneous action potentials, and therefore did not mimic the effect of acetylcholine. Conclusions: The chronotropic effects of bath applied acetylcholine and vagal stimulation are not principally the result of a suppression of if or iCa, whereas the activation of iK,ACh may play an important role.
KEYWORDS acetylcholine; sinoatrial node; heart
This work was supported by the British Council, the Royal Society, the British Heart Foundation and the Wellcome Trust.
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