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The weaver mutation changes the ion selectivity of the affected inwardly rectifying potassium channel GIRK2
Author(s) -
Tong Yanhe,
Wei Jianjun,
Zhang Shengwen,
Strong Judith A.,
Dlouhy Stephen R.,
Hodes M.E.,
Ghetti Bernardino,
Yu Lei
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00632-1
Subject(s) - chemistry , potassium channel , mutant , depolarization , kcsa potassium channel , g protein coupled inwardly rectifying potassium channel , substantia nigra , xenopus , biophysics , inward rectifier potassium ion channel , microbiology and biotechnology , ion channel , dopaminergic , receptor , biology , biochemistry , endocrinology , g protein , gene , dopamine
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.