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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.

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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
Authors :
NameEmailORCID
Chen, Yying.chen@surrey.ac.ukUNSPECIFIED
Chad, JEUNSPECIFIEDUNSPECIFIED
Cannon, RCUNSPECIFIEDUNSPECIFIED
Wheal, HVUNSPECIFIEDUNSPECIFIED
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 :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:35
Last Modified : 17 May 2017 14:43
URI: http://epubs.surrey.ac.uk/id/eprint/824341

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