ELECTRICAL EVENTS IN CARDIAC ADRENERGIC NERVES AND NORADRENALINE RELEASE FROM HEART INDUCED BY ACETYLCHOLINE AND KCL

The isolated cat heart with intact sympathetic nerve supply was perfused with varying concentrations of acetylcholine, DMPP and KCl. The ensuing asynchronous discharge in cardiac sympathetic nerves was recorded and the noradrenaline liberated into the perfusate was measured. The infusion of acetylcholine for one minute at a relatively low concentration (5×10-5 to 8×10-5 g/ml) induced asynchronous firing over the entire period of infusion and an average liberation of 44 ng/min noradrenaline. Increasing the concentration of acetylcholine or adding atropine to the perfusion fluid greatly shortened the duration of the antidromic discharge but enhanced severalfold the amount of noradrenaline liberated. Within a narrow range of very low concentrations DMPP induced continuous firing. At higher concentrations antidromic discharges were restricted to the first few seconds of infusion. Muscarinic drugs such as pilocarpine and methacholine neither induced firing nor released noradrenaline. When added to acetylcholine, pilocarpine reduced the amplitude of acetylcholine-evoked firing and the amount of noradrenaline liberated. KCl in concentrations above 50 mM induced a very short-lasting firing and a considerable noradrenaline output which was concentration-dependent. It is concluded that the acetylcholine- and DMPP-induced action potentials by themselves contribute little to the noradrenaline-releasing activity of these drugs. As in the case of KCl, the sustained depolarization of the sympathetic nerve ending by acetylcholine and DMPP seems to enhance entry of Ca++ into the ending, an essential factor for the liberation of noradrenaline. © 1968 Springer-Verlag.