KINETICS OF MUSCARINIC REDUCTION OF I-SAHP IN HIPPOCAMPAL-NEURONS - EFFECTS OF ACETYLCHOLINESTERASE INHIBITORS

The present experiments were designed to elucidate the time frame in w hich an evoked cholinergic impulse decreases the Ca2+-dependent K+ cur rent (I-sAHP) in hippocampal CA1 neurons, and to determine to what ext ent acetylcholinesterase (AChE) inhibitors enhance the efficacy of the cholinergic impulse. Whole cell voltage-clamp recordings were perform ed on hippocampal CAI neurons of rat brain slices and IsAHPS were evok ed by constant depolarizing pulses. Cholinergic afferent fibers in str atum 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 affer ent stimulus caused a profound decrease in the following I-sAHP only w hen the stimulus preceded the depolarizing pulse by 1-2 s. The stimulu s was without effects on the I-sAHP when applied greater than or equal to 5s before the depolarizing pulse. The effects of the afferent stim ulus were greatly enhanced in CA1 neurons exposed to the catalytic ACh E 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 greater than or equal to 30 s. However applications of peripheral site AChE inhibitors deca methonium and propidium caused only minor or no enhancement of the I-s AHP reduction after the afferent stimulus. We suggest in physiological conditions that muscarinic modulation of ionic conductances of CNS ne urons has a limited time course after a cholinergic impulse and that t he modulation is greatly enhanced and prolonged when catalytic activit ies of AChEs are suppressed pharmacologically.