4-Aminopyridine interrupts the modulation of acetylcholine release mediated by muscarinic and opiate receptors.

The effect of 4-aminopyridine, a potassium channel blocker on the muscarinic and opiate modulation of acetylcholine release, was investigated. Rat frontal cortical slices were loaded with [3H]choline, superfused continuously, and stimulated electrically. 4-Aminopyridine enhanced the stimulation-evoked release of tritium without affecting basal release. The electrically evoked release of radioactivity was reduced by the muscarinic agonist oxotremorine and the delta selective opiate receptor agonist Metenkephalin, and was enhanced in the presence of the cholinesterase inhibitor physostigmine by the muscarinic antagonist atropine. These effects were completely abolished by 4-aminopyridine. Since 4-aminopyridine blocks potassium permeability of the neuron, it is suggested that the changes in potassium permeability and the consequent alteration of membrane polarization are involved in the presynaptic modulation of acetylcholine release.