Impaired inhibition of epileptiform activity by baclofen, but not by adenosine in the weaver hippocampus

• Verfasst von: Jarolimek, Wolfgang [VerfasserIn]
• Verfasst von: Bäurle, Jörg [VerfasserIn]
• Verfasst von: Misgeld, Ulrich [VerfasserIn]
• Titel: Impaired inhibition of epileptiform activity by baclofen, but not by adenosine in the weaver hippocampus
• Verf.angabe: Wolfgang Jarolimek, Jörg Bäurle, Ulrich Misgeld
• Jahr: 2000
• Umfang: 8 S.
• Teil: volume:39
• Teil: year:2000
• Teil: number:2
• Teil: pages:246-253
• Teil: extent:8
• Fussnoten: Online 27 December 1999 ; Gesehen am 27.04.2021
• Titel Quelle: Enthalten in: Neuropharmacology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1970
• Jahr Quelle: 2000
• Band/Heft Quelle: 39(2000), 2, Seite 246-253
• ISSN Quelle: 1873-7064
• DOI: doi:10.1016/S0028-3908(99)00089-1
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: -baclofen
• Sach-SW: Adenosine
• Sach-SW: G protein-activated potassium currents
• Sach-SW: GABA receptors
• Sach-SW: Kir3.2
• K10plus-PPN: 1755985371

Abstract

The weaver defect results in a loss of baclofen- and adenosine-gated K+ conductance in the hippocampus of adult homozygous (wv/wv) mice. In addition, suppression of hippocampal epileptiform activity by baclofen is impaired (Jarolimek, W., Bäurle, J., Misgeld, U., 1998. Pore mutation in a G protein-gated inwardly rectifying K+ channel subunit causes loss of K+ dependent inhibition in weaver hippocampus. Journal of Neuroscience 18, 4001-4007). We used wv/wv and wild-type (+/+) mice to determine whether K+ conductance increases are essential for the suppression of epileptiform activity by R-baclofen and adenosine in disinhibited hippocampal slices. In wv/wv mice R-baclofen was less potent by two orders of magnitude in reducing the frequency of spontaneous synchronous burst discharges than in +/+ mice. Endogenous adenosine and adenosine A1 receptor agonists differed only slightly in their efficacy to inhibit spontaneous synchronous burst discharges in wv/wv and +/+ mice. The findings on adenosine A1 receptors suggest that the varied efficacy of R-baclofen in wv/wv and +/+ mice may not be explained solely on the basis of a loss of ligand-gated K+ conductance. Therefore, we investigated the affinity of GABAB receptors for the antagonist CGP55845A in wv/wv and +/+ hippocampi. Schild plot analysis revealed a KD for the GABAB antagonist CGP55845A 10 fold higher in wv/wv than in +/+ mice. The data suggest that an alteration of GABAB receptors could contribute to the reduced efficacy of R-baclofen to suppress hippocampal epileptiform activity in weaver mice, while the suppression by adenosine remains largely unaffected.