Astrocytes and Huntington's disease.
In this Viewpoint, we summarize and discuss the recent serendipitous discovery of an astrocyte Kir4.1 potassium channel dysfunction in two mouse models of Huntington's disease (HD). Restoration of Kir4.1 channels within astrocytes in vivo attenuated neuronal dysfunction, some aspects of motor dysfunction and increased survival time in a HD mouse model. Overall, the data show that aspects of altered neuronal excitability associated with HD may be secondary to changes in astrocyte-mediated K(+) homeostasis, thereby revealing a new striatal neural microcircuit mechanism in HD, and Kir4.1 channels and astrocytes as potential therapeutic targets for drug development.
Departments of Physiology, ‡Neurobiology, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, California 90095-1751, United States.
Baljit S
BS
Khakh
Michael V
MV
Sofroniew
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D003342:Corpus Striatum / Q000503:physiopathology; D004195:Disease Models, Animal; D005911:Gliosis / Q000503:physiopathology; D006816:Huntington Disease / Q000503:physiopathology*; D051379:Mice; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D000098854:Kcnj10 Channel
D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium