The muscarinic receptor and the hippocampus: An ionic channel analysis.
Item
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Title
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The muscarinic receptor and the hippocampus: An ionic channel analysis.
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Identifier
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AAI9304634
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identifier
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9304634
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Creator
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Benson, Deborah Mary.
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Contributor
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Sponsors: Thomas Frumkes | Emmanuel Landau
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Date
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1992
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Physiological | Biology, Neuroscience | Psychology, Psychobiology
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Abstract
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The effects of carbachol, a cholinergic agonist, on hippocampal pyramidal neurons were studied in tissue slices of both normal and denervated hippocampal pyramidal cells, utilizing intracellular electrophysiological recording techniques. The calcium-dependent potassium current (I{dollar}\sb{lcub}\rm AHP{rcub}{dollar}) and the voltage-dependent potassium current (I{dollar}\sb{lcub}\rm M{rcub}{dollar}) were both reversibly blocked by the application of carbachol (5-10 {dollar}\mu{dollar}M). Carbachol (1-10 {dollar}\mu{dollar}M) induced a steady inward current (or depolarization) under conditions in which both I{dollar}\sb{lcub}\rm AHP{rcub}{dollar} and I{dollar}\sb{lcub}\rm M{rcub}{dollar} were inactive. This effect of carbachol was reversed by atropine and blocked by pirenzepine, indicating that it is mediated by activation of an M{dollar}\sb1{dollar} muscarinic receptor. The carbachol effect was also blocked by potassium channel blockers cesium, tetraethylammonium and barium. Current-voltage (I-V) relationships were examined in carbachol and control conditions. In most cells, carbachol induced an inward current which reversed direction at a negative membrane potential. Furthermore, the reversal potentials induced by carbachol shifted in a positive direction when potassium concentration in the bath was increased. Thus, a primary effect of carbachol in these cells is blockage of a potassium leak channel.;In some cells, the carbachol-induced current did not reverse direction at a negative membrane potential. To examine further this effect, the effects of carbachol were compared to those of serotonin, which increases a "pure" potassium conductance, at varying potassium concentrations. Serotonin (10 {dollar}\mu{dollar}M) produced an outward current which reversed direction in each cell near the potassium equilibrium potential. The carbachol reversal potential values were negative relative to those of serotonin at 5 and 10 mM of potassium, but were not significantly different at 25 mM of potassium. Possible explanations for the anomalous carbachol effects, including a carbachol-induced dendritic conductance increase, are discussed.;Finally, the effects of carbachol were compared in voltage-clamped hippocampal pyramidal neurons obtained from normal and fimbria-fornix-lesioned rats. A significant increase in sensitivity to carbachol was seen in denervated neurons. This supersensitivity was demonstrated on both the inward leak current and I{dollar}\sb{lcub}\rm AHP{rcub}{dollar}. These findings provide evidence for cholinergic denervation supersensitivity in the hippocampus. Implications regarding the role of acetylcholine in learning/memory and disease are discussed.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
