Kinetics and Enhancement by Acetylcholinesterase Inhibitors of Muscarinic Synaptic Reduction of the Slow Ca2+-Dependent K+ Current in Rat Hippocampal CAl Neurons. Y. Zhang, P.L. Carlen and L. Zhang. Playfair Neuroscience Unit, Toronto Hospital Research Institute Departments of Medicine (Neurology) Bloorview Epilepsy Program, University of Toronto, Toronto, Ontario, Canada M5T 2S8.
APStracts 4:217N, 1997.
ABSTRACT
The present experiments were designed to elucidate the time frame in which an evoked cholinergic impulse decreases the Ca2+-dependent K+ current (IsAHP) in hippocampal CA1 neurons, and to determine to what extent acetylcholinesterase (AChE) inhibitors enhance the efficacy of the cholinergic impulse. Whole-cell voltage-clamp recordings were performed on hippocampal CA1 neurons of rat brain slices, and IsAHPs were evoked by constant depolarizing pulses. Cholinergic afferent fibers in stratum oriens were stimulated electrically, and the time interval between the afferent stimulus and the depolarizing pulse was varied from 1 to 30 seconds. In slices perfused with the standard external medium, the afferent stimulus caused a profound decrease in the following IsAHP only when the stimulus preceded the depolarizing pulse by 1-2 seconds. The stimulus was without effects on the IsAHP when applied ò5 seconds before the depolarizing pulse. The effects of the afferent stimulus were greatly enhanced in CA1 neurons exposed to the catalytic AChE inhibitors neostigmine, physostigmine or 9- amino-1,2,3,4-tetrahydro-acridine. A substantial decrease in the IsAHP was observed even when the stimulus preceded the depolarizing pulse by ò30 seconds. However, applications of peripheral site AChE inhibitors decamethonium and propidium caused a minor or no enhancement of the IsAHP reduction following the afferent stimulus. We suggest in physiological conditions that muscarinic modulation of ionic conductances of CNS neurons has a limited time course following a cholinergic impulse, and that the modulation is greatly enhanced and prolonged when catalytic activities of AChEs are suppressed pharmacologically. 

Received 7 March 1997; accepted in final form 29 August 1997.
APS Manuscript Number J198-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 5 September 1997