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• W2023730096 startingPage "353" @default.
• W2023730096 abstract "Miniature IPSCs recorded from cultured murine cerebellar granule cells increased in half‐width and amplitude following application of the benzodiazepine (BDZ) Flunitrazepam (Flu, 1 μ m ). The increase in the half‐width was much greater than that in the amplitude. Five‐millisecond applications of 1 m m GABA to nucleated outside‐out patches elicited rapidly rising biexponentially decaying responses that resembled IPSCs. Flu had no effect on the amplitude of such responses, but consistently slowed their deactivation by ∼50%. This effect was reversed by Flu washout or application of the BDZ antagonist Ro 15‐1788. The partial inverse agonist Ro15‐4513 speeded deactivation and depressed peak current amplitude by 23 ± 12%. The EC 50 for GABA was between 45 and 50 μ m . At submaximally effective agonist concentrations, Flu increased response amplitude and slowed response deactivation. Both effects were present in all cells taken from young cultures (4–7 days in vitro ) but the latter was absent in 55% of the neurones obtained from older cultures (14–27 days in vitro ). With 120 ms applications of 20 μ m GABA, responses activated monoexponentially (time constant, 39.8 ± 2.8 ms) and deactivated biexponentially (time constants, 40.4 ± 2.1 and 251 ± 15 ms). Application of Flu slowed both activation and deactivation. The latter effect arose from an increased contribution of the slower component of decay. Desensitization of responses to 1 m m GABA was biexponential, with time constants of 47 ± 11 and 479 ± 49 ms. Flu speeded desensitization by decreasing both fast and slow time constants. GABA A receptor desensitization consistently slowed subsequent deactivation. No significant relationship between the level of desensitization and the amount of slowing of deactivation produced by Flu was found. Responses to paired 5 ms applications of 1 m m GABA indicated that the slowing of deactivation and the speeding of desensitization produced by Flu combine to generate a marked frequency dependence in the actions of this BDZ. Thus when compared with control responses, GABA‐induced charge transfer was only enhanced by Flu during the first of two successive agonist applications." @default.
• W2023730096 created "2016-06-24" @default.
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• W2023730096 date "1997-09-01" @default.
• W2023730096 modified "2023-10-15" @default.
• W2023730096 title "Frequency-Dependent Actions of Benzodiazepines on GABA_AReceptors in Cultured Murine Cerebellar Granule Cells" @default.
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• W2023730096 doi "https://doi.org/10.1111/j.1469-7793.1997.353bh.x" @default.
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