Muscarinic inhibition of potassium-induced noradrenaline release and its dependence on the calcium concentration.

1. Noradrenaline release from the isolated rabbit heart was evoked by perfusion with a medium containing 135 mM potassium and 17 mM sodium ions (high K+-low Na+). 2. The noradrenaline output in response to high K+-low Na+ was dose-dependently decreased by methacholine (0.625-320 muM) and this effect was reserved by atropine 1.44 mM. 3. Lowering the calcium concentration of high K+-low Na+ from 1.8-0.1125 mM decreased the noradrenaline output by 85%. The effect of methacholine, expressed as % inhibition of noradrenaline release, was potentiated by lowering of the calcium concentration. 4. Both at normal and lowered calcium concentrations the inhibitory action of methacholine was larger from 0-5 than from 5-10 min after perfusion with high K+-low Na+. 5. Perfusion of hearts with media containing high K+-low Na+ or normal K+-low Na+ caused noradrenaline outputs somewhat smaller than those after high K+-low Na+. The release from 0-5 min was both calcium-dependent and inhibited by methacholine. 6. High K+ and/or low Na+ solutions caused an increase in coronary perfusion pressure which was little affected by the noradrenaline released simultaneously. 7. It is concluded that activation of muscarine receptors at the terminal adrenergic fibre decreases the availability of calcium for transmitter release.