Insulin-like growth factor 1 and a cytosolic tyrosine kinase activate chloride outward transport during maturation of hippocampal neurons

Wolfgang Kelsch, Sheriar Hormuzdi, Emine Straube, Andrea Lewen, Hannah Monyer, Ulrich Misgeld

    Research output: Contribution to journalArticlepeer-review

    131 Citations (Scopus)

    Abstract

    The development of hyperpolarizing inhibition is an important step in the maturation of neuronal networks. Hyperpolarizing inhibition requires Cl- outward transport that is accomplished by KCC2, a K+/Cl- cotransporter. We show that cultured hippocampal neurons initially contain an inactive form of the KCC2 protein, which becomes activated during subsequent maturation of the neurons. We also show that this process is accelerated by transient stimulation of IGF-1 receptors. Because the transporter can be rapidly activated by coapplication of IGF-1 and an Src kinase and can be deactivated by membrane-permeable protein tyrosine kinase inhibitors, we suggest that activation of K+/Cl- cotransporter function by endogenous protein tyrosine kinases mediates the developmental switch of GABAergic responses to hyperpolarizing inhibition.
    Original languageEnglish
    Pages (from-to)8339-8347
    Number of pages9
    JournalJournal of Neuroscience
    Volume21
    Issue number21
    Publication statusPublished - Nov 2001

    Keywords

    • Development
    • Furosemide
    • GABAA
    • Genistein
    • Hippocampus
    • IGF-1
    • KCC2
    • Tyrosine kinase
    • Chlorides metabolism
    • Insulin-like growth factor I metabolism
    • Ion transport physiology
    • Neurons metabolism
    • Protein-tyrosine kinases metabolism

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