Glucose concentration inversely alters neocortical slice excitability through an osmotic effect.
Neurological problems can develop when blood glucose levels rapidly rise or fall yet there has been little experimentation at a cellular level to assess how neurophysiological change may be induced. Using intracellular recording in the rat neocortical slice preparation, we examined pyramidal neurons of layers II-III as saline D-glucose concentration was altered. Single cell properties, synaptic transmission and epileptiform discharges were studied in control saline and compared with corresponding data when osmolality was raised with D-glucose by 20-80 mOsm. Although single cell properties were not significantly altered, the amplitude of evoked early and late EPSPs were proportionally reduced within 5 min. A similar but more pronounced effect was observed with mannitol, whereas freely permeable dimethylsulfoxide (DMSO) was without effect. Hyposmolality increased the amplitude of evoked early and late EPSPs. Therefore the dampening of synaptic transmission by D-glucose appears osmotic in origin. D-glucose was osmotically effective only above 30 mM probably because it is cell-permeable at lower concentrations. In slices made epileptogenic by Mg(2+)-free saline, increasing D-glucose decreased the frequency and increased the duration of interictal bursts. Again mannitol mimicked the glucose effects and hyposmotic change gave opposing responses. The inverse relation between glucose concentration and neocortical excitability correlates well with clinical observations that an acute reduction in blood glucose from hyperglycemic levels (as follows insulin over-administration) can evoke generalized seizure.
Department of Anatomy Queen's University, Kingston, Ontario, Canada.
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Rosen
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Andrew
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004285:Dogs; D005071:Evoked Potentials / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D008353:Mannitol / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis
D008353:Mannitol; D005947:Glucose; D004121:Dimethyl Sulfoxide