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Schizophr Bull. 2016 Jan;42(1):191-201. doi: 10.1093/schbul/sbv105. Epub 2015 Aug 3.

AMIGO-Kv2.1 Potassium Channel Complex Is Associated With Schizophrenia-Related Phenotypes.

Author information

1
Neuroscience Center, University of Helsinki, Helsinki, Finland; marjaana.kiiltomaki@helsinki.fi.
2
Neuroscience Center, University of Helsinki, Helsinki, Finland;
3
Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland;
4
Division of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland;
5
Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland;
6
Neuroscience Center, University of Helsinki, Helsinki, Finland; Department of Biosciences, University of Helsinki, Helsinki, Finland; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland;
7
Neuroscience Center, University of Helsinki, Helsinki, Finland; Department of Biosciences, University of Helsinki, Helsinki, Finland;
8
Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland;
9
Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland.

Abstract

The enormous variability in electrical properties of neurons is largely affected by a multitude of potassium channel subunits. Kv2.1 is a widely expressed voltage-dependent potassium channel and an important regulator of neuronal excitability. The Kv2.1 auxiliary subunit AMIGO constitutes an integral part of the Kv2.1 channel complex in brain and regulates the activity of the channel. AMIGO and Kv2.1 localize to the distinct somatodendritic clusters at the neuronal plasma membrane. Here we have created and characterized a mouse line lacking the AMIGO gene. Absence of AMIGO clearly reduced the amount of the Kv2.1 channel protein in mouse brain and altered the electrophysiological properties of neurons. These changes were accompanied by behavioral and pharmacological abnormalities reminiscent of those identified in schizophrenia. Concomitantly, we have detected an association of a rare, population-specific polymorphism of KV2.1 (KCNB1) with human schizophrenia in a genetic isolate enriched with schizophrenia. Our study demonstrates the involvement of AMIGO-Kv2.1 channel complex in schizophrenia-related behavioral domains in mice and identifies KV2.1 (KCNB1) as a strong susceptibility gene for schizophrenia spectrum disorders in humans.

KEYWORDS:

AMIGO; KCNB1; Kv2.1; mouse behavior; susceptibility gene

PMID:
26240432
PMCID:
PMC4681558
DOI:
10.1093/schbul/sbv105
[Indexed for MEDLINE]
Free PMC Article

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