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• W1602151323 startingPage "4946" @default.
• W1602151323 abstract "Background and Purpose The K v 7 channel activator flupirtine is a clinical analgesic characterized as ‘selective neuronal potassium channel opener’. Flupirtine was found to exert comparable actions at GABA A receptors and K v 7 channels in neurons of pain pathways, but not in hippocampus. Experimental Approach Expression patterns of GABA A receptors were explored in immunoblots of rat dorsal root ganglia, dorsal horns and hippocampi using antibodies for 10 different subunits. Effects of flupirtine on recombinant and native GABA A receptors were investigated in patch clamp experiments and compared with the actions on K v 7 channels. Key Results Immunoblots pointed towards α2, α3, β3 and γ2 subunits as targets, but in all γ2‐containing receptors the effects of flupirtine were alike: leftward shift of GABA concentration‐response curves and diminished maximal amplitudes. After replacement of γ2S by δ, flupirtine increased maximal amplitudes. Currents through α1β2δ receptors were more enhanced than those through K v 7 channels. In hippocampal neurons, flupirtine prolonged inhibitory postsynaptic currents, left miniature inhibitory postsynaptic currents (mIPSCs) unaltered and increased bicuculline‐sensitive tonic currents; penicillin abolished mIPSCs, but not tonic currents; concentration‐response curves for GABA‐induced currents were shifted to the left by flupirtine without changes in maximal amplitudes; in the presence of penicillin, maximal amplitudes were increased; GABA‐induced currents in the presence of penicillin were more sensitive towards flupirtine than K + currents. In dorsal horn neurons, currents evoked by the δ‐preferring agonist THIP (gaboxadol) were more sensitive towards flupirtine than K + currents. Conclusions and Implications Flupirtine prefers δ‐containing GABA A receptors over γ‐containing ones and over K v 7 channels." @default.
• W1602151323 created "2016-06-24" @default.
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• W1602151323 date "2015-10-01" @default.
• W1602151323 modified "2023-10-14" @default.
• W1602151323 title "δ Subunit-containing GABA_A receptors are preferred targets for the centrally acting analgesic flupirtine" @default.
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• W1602151323 doi "https://doi.org/10.1111/bph.13262" @default.
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