The weaver mutation changes the ion selectivity of the affected inwardly rectifying potassium channel GIRK2

Yanhe Tong, Jianjun Wei, Shengwen Zhang, Judith A. Strong, Stephen Dlouhy, M. E. Hodes, Bernardino Ghetti, Lei Yu

Research output: Contribution to journalArticle

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Abstract

The weaver mutation in mice has recently been identified as a single base-pair mutation in the Girk2 gene, which encodes a G-protein-activated inwardly rectifying potassium channel, GIRK2. The mutation results in a Gly to Ser substitution at residue 156, in the putative pore-forming region of the potassium channel. In the present study, we used Xenopus oocytes to express mutant GIRK2, and to characterize the effects of the mutation on the channel. The mutation results in a loss of the normal high selectivity for K+ over Na+, with little effect on other channel properties such as activation by the mu opioid receptor. The resulting increase in basal Na+ permeability causes a marked depolarization of oocytes expressing the mutant GIRK2 protein. This result was observed even when the mutant GIRK2 was coexpressed with GIRK1, a situation more analogous to that seen in vivo. Thus, the increased Na+ permeability and resulting depolarization may contribute to the pathology of cerebellar granule cells and substantia nigra dopaminergic neurons observed in the weaver mice.

Original languageEnglish
Pages (from-to)63-68
Number of pages6
JournalFEBS Letters
Volume390
Issue number1
DOIs
StatePublished - Jul 15 1996

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Inwardly Rectifying Potassium Channel
Depolarization
Ions
Mutation
mu Opioid Receptor
Potassium Channels
Pathology
GTP-Binding Proteins
Neurons
Substitution reactions
Genes
Chemical activation
Oocytes
Permeability
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Neurologic Mutant Mice
Dopaminergic Neurons
Substantia Nigra
Mutant Proteins
Xenopus

Keywords

  • G-protein-coupled K channel
  • Ion permeability
  • Oocyte
  • Potassium channel

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The weaver mutation changes the ion selectivity of the affected inwardly rectifying potassium channel GIRK2. / Tong, Yanhe; Wei, Jianjun; Zhang, Shengwen; Strong, Judith A.; Dlouhy, Stephen; Hodes, M. E.; Ghetti, Bernardino; Yu, Lei.

In: FEBS Letters, Vol. 390, No. 1, 15.07.1996, p. 63-68.

Research output: Contribution to journalArticle

Tong, Yanhe ; Wei, Jianjun ; Zhang, Shengwen ; Strong, Judith A. ; Dlouhy, Stephen ; Hodes, M. E. ; Ghetti, Bernardino ; Yu, Lei. / The weaver mutation changes the ion selectivity of the affected inwardly rectifying potassium channel GIRK2. In: FEBS Letters. 1996 ; Vol. 390, No. 1. pp. 63-68.
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AU - Hodes, M. E.

AU - Ghetti, Bernardino

AU - Yu, Lei

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