The cholinergic pharmacology of hippocampal pyramidal cells: A microiontophoretic study

It was concluded that hippocampal pyramidal cells are responsive to muscarinic and some nicotinic agents and these agents are not acting at two independent receptors since there is crossover between Nicotinic antagonists and mus carinic agonists.

Abstract

The purpose of this study was to examine the pharmacological properties of an identified cholinergic system in the CNS of the rat. The responses of hippocampal pyramidal cells to the microiontophoretic application of various nicotinic and muscarinic agents were monitored via extracellular recording. In addition, interactions between musearinic and nicotinic compounds were investigated. Acetylcholine and carbachol, agents effective at both nicotinic and muscarinic sites, readily produced excitation of hippocampal pyramidal cells. The muscarinic agonists muscarine, acetyl-β-methylcholine and bethanechol also excited these cells at low iontophoretic currents. The muscarinic antagonists scopolamine and quinuclidinyl benzilate totally blocked acetylcholine excitation of pyramidal cells without altering their excitation by glutamate. Hippocampal pyramidal cells were also responsive to certain nicotinic compounds. The nicotinic agonist phenyltrimethylammonium caused excitation of pyramidal cells. The putative nicotinic agonist tetramethylammonium and the nicotinic antagonists dihydro-β-erythroidine and gallamine specifically blocked acetylcholine excitation of these cells. However, other nicotinic agents investigated produced a nonspecific block of acetylcholine excitation in that the response to glutamate was also affected. The classical nicotinic antagonist (+)-tubocurarine produced no effect in the amounts tested. In addition, the nicotinic antagonists dihydro-β-erythroidine and gallamine also completely blocked the excitation of pyramidal cells by the muscarinic agonists muscarine and acetyl-β-methylcholine. It was concluded that: (1) hippocampal pyramidal cells are responsive to muscarinic and some nicotinic agents and (2) these agents are not acting at two independent receptors since there is crossover between nicotinic antagonists and muscarinic agonists.