An electrophysiological action of acetylcholinesterase independent of its catalytic site

Summary

Acetylcholinesterase (AChE) is released from the cell bodies and/or dendrites of dopaminergic neurones in the substantia nigra. Extracellular AChE can modify both the electrical activity of dopaminergic nigral neurones and the associated motor behaviour of the animal. These effects seem to be unrelated to hydrolysis of acetylcholine, but the underlying cellular mechanisms of these actions of AChE are unknown. The possible non-cholinergic action of AChE on the membrane properties of dopaminergic neurones was thus investigated by intracellular recording from midbrain slices in vitro. Application of AChE resulted in a marked hyperpolarization of the membrane accompanied by a decrease in input resistance, sometimes preceded by a period of spontaneous firing. Butyrylcholinesterase (BuChE) was without effect. AChE pre-treated with an irreversible inhibitor (Soman) of its enzymic activity caused similar changes to those seen following administration of untreated AChE. It is concluded that AChE can modify the membrane properties of nigrostriatal neurones in a way that is independent of its ability to hydrolyse acetylcholine. This novel biological property of AChE provides a possible mechanism by which this neurosecretory protein could modulate the functioning of the neurones from which it is secreted and suggests that other ‘non-cholinergic’ actions of AChE might exist.