Cellular mechanisms of the neurotoxicity caused by hyperammonemia and hypoglycemia.
Date
1992
Authors
Fan, Ping.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
Hyperammonemia and hypoglycemia are metabolic disorders which interfere with the function of the central nervous system. Cellular mechanisms of disturbed neuronal function in these two conditions were investigated in rat hippocampal slices with the use of extracellular and intracellular recording.
Synaptic transmission from Schaffer-collaterals to CA1 pyramidal neurons was diminished by as little as 0.5 mM NH$\sb4$Cl. During the presence of 1-4 mM NH$\sb4\sp+,$ brain concentrations seen in hepatic encephalopathy, the membrane potential of CA1 neurons depolarized with no significant change in input resistance. Quisqualate-induced inward currents, which were sensitive to CNQX, were blocked, glutamate-induced currents were slightly reduced, while NMDA-induced currents were greatly facilitated.
Low glucose concentrations (0.2-1 mM) seen in hypoglycemia caused mostly biphasic membrane potential changes: a small initial hyperpolarization followed by a large depolarization. Occasionally only one of these potential changes was observed. Input resistance of the neurons always decreased. Low glucose also interfered with synaptic transmission: first the generation of action potentials by EPSPs was inhibited, while later the size of EPSPs decreased. Quisqualate and NMDA currents were first potentiated, then inhibited.
Results suggest that NH$\sb4\sp+$ depresses transmission by eliminating quisqualate-induced responses that are mainly responsible for EPSPs, while low glucose probably shunts EPSPs so that they can no longer generate action potentials at the axon hillock. This impairment in synaptic transmission is likely to contribute to neurological abnormalities seen in hyperammonemia and hypoglycemia.
Thesis (Ph.D.)--Dalhousie University (Canada), 1992.
Synaptic transmission from Schaffer-collaterals to CA1 pyramidal neurons was diminished by as little as 0.5 mM NH$\sb4$Cl. During the presence of 1-4 mM NH$\sb4\sp+,$ brain concentrations seen in hepatic encephalopathy, the membrane potential of CA1 neurons depolarized with no significant change in input resistance. Quisqualate-induced inward currents, which were sensitive to CNQX, were blocked, glutamate-induced currents were slightly reduced, while NMDA-induced currents were greatly facilitated.
Low glucose concentrations (0.2-1 mM) seen in hypoglycemia caused mostly biphasic membrane potential changes: a small initial hyperpolarization followed by a large depolarization. Occasionally only one of these potential changes was observed. Input resistance of the neurons always decreased. Low glucose also interfered with synaptic transmission: first the generation of action potentials by EPSPs was inhibited, while later the size of EPSPs decreased. Quisqualate and NMDA currents were first potentiated, then inhibited.
Results suggest that NH$\sb4\sp+$ depresses transmission by eliminating quisqualate-induced responses that are mainly responsible for EPSPs, while low glucose probably shunts EPSPs so that they can no longer generate action potentials at the axon hillock. This impairment in synaptic transmission is likely to contribute to neurological abnormalities seen in hyperammonemia and hypoglycemia.
Thesis (Ph.D.)--Dalhousie University (Canada), 1992.
Keywords
Biology, Neuroscience., Biology, Animal Physiology., Biophysics, General.