The Journal of Neurophysiology Vol. 78 No. 6 December 1997, pp. 2999-3007
Copyright ©1997 The American Physiological Society

Kinetics of Muscarinic Reduction of I_sAHP in Hippocampal Neurons: Effects of Acetylcholinesterase Inhibitors

Y. Zhang, P. L. Carlen, and L. Zhang

Playfair Neuroscience Unit, Departments of Medicine (Neurology), Toronto Hospital Research Institute, Bloorview Epilepsy Program, University of Toronto, Toronto, Ontario M5T 2S8, Canada

Zhang, Y., P. L. Carlen, and L. Zhang. Kinetics of muscarinic reduction of I_sAHP in hippocampal neurons: effects of acetylcholinesterase inhibitors. J. Neurophysiol. 78: 2999-3007, 1997. The present experiments were designed to elucidate the time frame in which an evoked cholinergic impulse decreases the Ca²⁺-dependent K⁺ current (I_sAHP) 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 I_sAHPs 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 s. In slices perfused with the standard external medium, the afferent stimulus caused a profound decrease in the following I_sAHP only when the stimulus preceded the depolarizing pulse by 1-2 s. The stimulus was without effects on the I_sAHP when applied 5s 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 I_sAHP was observed even when the stimulus preceded the depolarizing pulse by 30 s. However applications of peripheral site AChE inhibitors decamethonium and propidium caused only minor or no enhancement of the I_sAHP reduction after the afferent stimulus. We suggest in physiological conditions that muscarinic modulation of ionic conductances of CNS neurons has a limited time course after a cholinergic impulse and that the modulation is greatly enhanced and prolonged when catalytic activities of AChEs are suppressed pharmacologically.

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