IONIC BASIS OF THE CHRONOTROPIC EFFECT OF ACETYLCHOLINE ON THE RABBITSINOATRIAL NODE

Objective: The aim was to study the ionic basis of the chronotropic ef fects of bath applied acetylcholine and vagal stimulation on the rabbi t sinoatrial node. Methods: The chronotropic effect of bath applied ac etylcholine was measured in single cells and small multicellular prepa rations from the rabbit sinoatrial node and the chronotropic effect of postganglionic vagal stimulation was measured in the intact sinoatria l node. The roles of the hyperpolarisation activated current, i(f), th e acetylcholine activated potassium current, i(K,ACh), and the L-type calcium current, i(Ca), were investigated by blocking the currents wit h 1-2 mM Cs+ or 10(-6) M UL-FS49, 0.2-1.0 mM Ba2+, and 6 X 10(-6) M ni fedipine, respectively. Results: Under control conditions, small multi cellular preparations were approximately two orders of magnitude less sensitive to bath applied acetylcholine than single cells. However, af ter block of acetylcholinesterase by eserine in small multicellular pr eparations the sensitivities of the two types of preparation were appr oximately the same. Block of i(f) either had no discernible effect or increased the chronotropic effect of bath applied acetylcholine on sin gle cells or small multicellular preparations, whereas partial block o f i(K,ACh) reduced it substantially. Similarly, block of i(f) did not suppress the initial slowing of spontaneous action potentials by vagal stimulation, whereas partial block of i(K,ACh) reduced it. The hyperp olarisation of the arrested sinoatrial node in response to vagal stimu lation was also substantially reduced by block of i(K,ACh). Partial bl ock of i(Ca) caused large decreases in the action potential amplitude and maximum diastolic potential, but little decrease in the rate of sp ontaneous 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 i(f) or i(Ca), whereas the activation of i(K,ACh) may play an important role.