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Defective γ-aminobutyric acid type B receptor-activated inwardly rectifying K + currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice
Author(s) -
Paul A. Slesinger,
Markus Stoffel,
Yuh Nung Jan,
Yuh Nung Jan
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.22.12210
Subject(s) - g protein coupled inwardly rectifying potassium channel , microbiology and biotechnology , receptor , potassium channel , g protein , patch clamp , chemistry , ion channel , inward rectifier potassium ion channel , biology , biophysics , biochemistry
Stimulation of inhibitory neurotransmitter receptors, such as γ-aminobutyric acid type B (GABAB ) receptors, activates G protein-gated inwardly rectifying K+ channels (GIRK) which, in turn, influence membrane excitability. Seizure activity has been reported in aGirk2 null mutant mouse lacking GIRK2 channels but showing normal cerebellar development as well as in theweaver mouse, which has mutated GIRK2 channels and shows abnormal development. To understand how the function of GIRK2 channels differs in these two mutant mice, we compared the G protein-activated inwardly rectifying K+ currents in cerebellar granule cells isolated fromGirk2 null mutant andweaver mutant mice with those from wild-type mice. Activation of GABAB receptors in wild-type granule cells induced an inwardly rectifying K+ current, which was sensitive to pertussis toxin and inhibited by external Ba2+ ions. The amplitude of the GABAB receptor-activated current was severely attenuated in granule cells isolated from bothweaver andGirk2 null mutant mice. By contrast, the G protein-gated inwardly rectifying current and possibly the agonist-independent basal current appeared to be less selective for K+ ions inweaver but notGirk2 null mutant granule cells. Our results support the hypothesis that a nonselective current leads to theweaver phenotype. The loss of GABAB receptor-activated GIRK current appears coincident with the absence of GIRK2 channel protein and the reduction of GIRK1 channel protein in theGirk2 null mutant mouse, suggesting that GABAB receptors couple to heteromultimers composed of GIRK1 and GIRK2 channel subunits.

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