Reduced Mg2+ blockade of synaptically activated N-methyl-D-aspartate receptor-channels in CA1 pyramidal neurons in kainic acid-lesioned rat hippocampus.

Chen, Y, Chad, JE, Cannon, RC and Wheal, HV (1999) Reduced Mg2+ blockade of synaptically activated N-methyl-D-aspartate receptor-channels in CA1 pyramidal neurons in kainic acid-lesioned rat hippocampus. Neuroscience, 88 (3). pp. 727-739.

Full text not available from this repository.

Abstract

Unilateral kainic acid lesion in the hippocampus caused a long-term change in the balance between excitatory and inhibitory drive onto CA1 pyramidal cells, making these cells hyperexcitable several weeks post-lesion. In this study, we have shown an enhanced N-methyl-D-aspartate receptor-mediated component in the excitatory synaptic transmission together with a reduced GABA(A) receptor-mediated inhibition in CA1 pyramidal cells one-week post kainic acid lesion. In these cells, pharmacologically isolated N-methyl-D-aspartate receptor-mediated whole-cell excitatory postsynaptic currents were significantly larger at negative holding potentials, and the voltage-dependence of N-methyl-D-aspartate receptor channels was shifted in the hyperpolarizing direction. The plot of relative conductance (g/gMax) shifted significantly (P<0.01) to more negative holding potentials by 19 mV (-28+/-4 mV in control slices and -47+/-4 mV in kainic acid slices) at the half maximal conductance point (g/gMax =0.5). This shift gives a larger N-methyl-D-aspartate receptor-mediated component in the excitatory synaptic transmission at resting membrane potentials (around -60 mV). The shifted voltage dependence is highly sensitive to extracellular Mg2+ ions. Moderate increases in [Mg2+]o from 1 mM to 2.6 mM more than compensated for the negative shift and effectively suppressed the population epileptiform bursting activity. Fitting the voltage dependence to an ionic block model revealed a higher dissociation constant of N-methyl-D-aspartate receptor channels for Mg2+ in kainic acid-lesioned slices (52 mM at 0 mV; 330 microM at -60 mV) than in control slices (7.7 mM at 0 mV; 93 microM at -60 mV). While a simple single site model adequately fitted the control data for [Mg2+]o at 1 mM and 2.6 mM, no consistent model of this form was found for the kainic acid-lesioned slices. These results revealed changed properties of N-methyl-D-aspartate receptor channels in the kainic acid-lesioned model of epilepsy. The reduced Mg2+ blockade of N-methyl-D-aspartate receptor channels contributed significantly to the epileptiform bursting activity.

Item Type:	Article
Divisions :	Surrey research (other units)
Authors :	Name Email ORCID Chen, Y ying.chen@surrey.ac.uk Chad, JE Cannon, RC Wheal, HV
Date :	1999
Uncontrolled Keywords :	2-Amino-5-phosphonovalerate, Animals, Electric Stimulation, Evoked Potentials, Hippocampus, In Vitro Techniques, Kainic Acid, Lidocaine, Magnesium, Male, Models, Neurological, Patch-Clamp Techniques, Pyramidal Cells, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate, Reference Values, Synaptic Transmission, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 09:35
Last Modified :	24 Jan 2020 17:15
URI:	http://epubs.surrey.ac.uk/id/eprint/824341

Actions (login required)

View Item

Downloads