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- W2051208171 abstract "Ionotropic glutamate receptor‐mediated responses were recorded from rat magnocellular basal forebrain neurones under voltage clamp from a somatically located patch‐clamp pipette. Currents were recorded from both acutely dissociated neurones and neurones maintained in culture for up to 6 weeks. Non‐NMDA and NMDA receptor‐mediated events could be distinguished pharmacologically using the selective agonists ( S )‐α‐amino‐3‐hydroxy‐5‐methyl‐isoxazolepropionic acid (AMPA), kainate and N ‐methyl‐D‐aspartate (NMDA), and antagonists 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and D(‐)‐2‐amino‐5‐phosphonopentanoic acid (AP5). Responses to rapid application of AMPA displayed pronounced and rapid desensitization. Responses to kainate showed no desensitization. Steady‐state EC 50 values for AMPA and kainate were 2.7 ± 0.4 μM ( n = 5 ) and 138 ± 25 μM ( n = 10 ), respectively. Cyclothiazide markedly increased current amplitude of responses to both agonists, whereas concanavalin A had no clear effect on either response. The selective AMPA receptor antagonist GYKI 53655 inhibited responses to kainate with an IC 50 of 1.2 ± 0.08 μM ( n = 5 ) at ‐70 mV. These data strongly suggest that AMPA receptors are the predominant non‐NMDA receptors expressed by basal forebrain neurones. At ‐70 mV, approximately 6 % of control current amplitude remained, at a maximally effective concentration of GYKI 53655. This residual response displayed desensitization, was insensitive to cyclothiazide and was potentiated by concanavalin A, suggesting that it was mediated by a kainate receptor. Current‐voltage relationships for non‐NMDA receptor‐mediated currents were obtained from both nucleated patches pulled from neurones in culture and from acutely dissociated neurones. With 30 μM spermine in the recording pipette, currents frequently displayed double‐rectification characteristic of non‐NMDA receptors with high Ca 2+ permeabilities. Ca 2+ permeability, relative to Na + and Cs + , was investigated using constant field theory. The measured Ca 2+ to Na + permeability coefficient ratio was 0.26‐3.6; median, 1.27 ( n = 15 ). Current flow through non‐NMDA receptors was inhibited by Ca 2+ , Cd 2+ and Co 2+ ions. At a holding potential of ‐70 mV, a maximally effective concentration of Cd 2+ (> 30 mM) reduced current amplitude by approximately 90 %, with an IC 50 of 44 μM. In six out of seven cells tested, block by Cd 2+ was voltage sensitive. Ca 2+ permeability of many of the non‐NMDA receptors expressed by magnocellular basal forebrain neurones may underlie the unusual sensitivity of cholinergic basal forebrain neurones to non‐NMDA receptor‐mediated excitotoxicity." @default.
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- W2051208171 date "1998-04-01" @default.
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- W2051208171 title "Ca<sup>2+</sup>-permeable non-NMDA glutamate receptors in rat magnocellular basal forebrain neurones" @default.
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- W2051208171 doi "https://doi.org/10.1111/j.1469-7793.1998.453bq.x" @default.
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