ArticleThe Journal of biological chemistry2010
Molecular mechanisms of EAST/SeSAME syndrome mutations in Kir4.1 (KCNJ10).
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- WONOEP XVII appraisal: Targeting network excitability beyond the synapse -Neurotransmitter, ionic, and electro -diffusions.Epilepsia · 2025Review
- Role of Glyoxalase in Astrocytes' Supportive Function Under Hyperglycemic Conditions: Aminoguanidine and Kir4.1 Channel Recovery.Brain sciences · 2025Article
- Juvenile Dystonia Associated with Heterozygous Missense Variant in KCNJ10.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Spermidine Synthase Localization in Retinal Layers: Early Age Changes.International journal of molecular sciences · 2024Article
- Article
- Spinocerebellar ataxia in the Bouvier des Ardennes breed is caused by a KCNJ10 missense variant.Journal of veterinary internal medicine · 2023Article
- Advances in Zebrafish as a Comprehensive Model of Mental Disorders.Depression and anxiety · 2023Review
- Aglycosylated extracellular loop of inwardly rectifying potassium channel 4.1 (KCNJ10) provides a target for autoimmune neuroinflammation.Brain communications · 2023Article
- Characterizing Genotypes and Phenotypes Associated with Dysfunction of Channel-Encoding Genes in a Cohort of Patients with Intellectual Disability.Archives of Iranian medicine · 2022Article
- Inwardly rectifying KAmerican journal of physiology. Cell physiology · 2022Review
- Emerging Roles of Astrocyte Kir4.1 Channels in the Pathogenesis and Treatment of Brain Diseases.International journal of molecular sciences · 2021Review
- Inwardly rectifying potassium channel 5.1: Structure, function, and possible roles in diseases.Genes & diseases · 2021Review
- Structure and Functions of Gap Junctions and Their Constituent Connexins in the Mammalian CNS.Biochemistry (Moscow) Supplement. Series A, Membrane and cell biology · 2021Article
- Deletion ofFrontiers in cell and developmental biology · 2021Article
- Exploring Neuronal Vulnerability to Head Trauma Using a Whole Exome Approach.Journal of neurotrauma · 2020Article
- Expression, localization, and functional properties of inwardly rectifying KAmerican journal of physiology. Renal physiology · 2020Review
- Downregulation of Astrocytic Kir4.1 Potassium Channels Is Associated with Hippocampal Neuronal Hyperexcitability in Type 2 Diabetic Mice.Brain sciences · 2020Article
- Role of Astrocytic Inwardly Rectifying Potassium (Kir) 4.1 Channels in Epileptogenesis.Frontiers in neurology · 2020Review
- Astroglial Mechanisms of Ketamine Action Include Reduced Mobility of Kir4.1-Carrying Vesicles.Neurochemical research · 2020Review
- Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and activation of microglia and astrocytes in mouse hippocampus.Neurobiology of disease · 2019Article
3 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
Inwardly rectifying potassium channel Kir4.1 is critical for glial function, control of neuronal excitability, and systemic K(+) homeostasis. Novel mutations in Kir4.1 have been associated with EAST/SeSAME syndrome, characterized by mental retardation, ataxia, seizures, hearing loss, and renal salt waste. Patients are homozygous for R65P, G77R, C140R or T164I; or compound heterozygous for A167V/R297C or R65P/R199Stop, a deletion of the C-terminal half of the protein. We investigated the functional significance of these mutations by radiotracer efflux and inside-out membrane patch clamping in COSm6 cells expressing homomeric Kir4.1 or heteromeric Kir4.1/Kir5.1 channels. All of the mutations compromised channel function, but the underlying mechanisms were different. R65P, T164I, and R297C caused an alkaline shift in pH sensitivity, indicating that these positions are crucial for pH sensing and pore gating. In R297C, this was due to disruption of intersubunit salt bridge Glu(288)-Arg(297). C140R breaks the Cys(108)-Cys(140) disulfide bond essential for protein folding and function. A167V did not affect channel properties but may contribute to decreased surface expression in A167V/R297C. In G77R, introduction of a positive charge within the bilayer may affect channel structure or gating. R199Stop led to a dramatic decrease in surface expression, but channel activity was restored by co-expression with intact subunits, suggesting remarkable tolerance for truncation of the cytoplasmic domain. These results provide an explanation for the molecular defects that underlie the EAST/SeSAME syndrome.
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