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Regulation of Myo-Inositol Homeostasis in Differentiated Human NT2-N Neurons

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Abstract

We have investigated the possible role of second messengers on inositol homeostasis in NT2-N cells, human central nervous system neurons obtained by terminal differentiation of teratocarcinoma precursors. Uptake of inositol into NT2-N neurons was inhibited ∼10% by protein kinase C (PKC) activation but was unaffected by either the presence of cyclic nucleotide analogs or changes in the intracellular concentration of Ca2+. Efflux of inositol from NT2-N neurons was enhanced in hypotonic buffer but virtually eliminated by inclusion of the Cl− channel blocker 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, a result which indicates the involvement of a volume-sensitive organic osmolyte-anion channel. Volume-sensitive inositol efflux was stimulated ∼30% following activation of PKC or elevation of the cytosolic Ca2+ concentration but was unaffected by protein kinase A activation. These results suggest that whereas inositol uptake into NT2-N neurons is relatively refractory to regulation, volume-sensitive inositol efflux may be significantly affected by intracellular signaling events.

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Authors and Affiliations

  1. Neuroscience Laboratory and Mental Health Research Institute, University of Michigan, Ann Arbor, MI

    James E. Novak, Bernard W. Agranoff & Stephen K. Fisher

  2. University of Michigan, Ann Arbor, MI

    James E. Novak & Bernard W. Agranoff

  3. Department of Pharmacology, University of Michigan, Ann Arbor, MI

    Stephen K. Fisher

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Novak, J.E., Agranoff, B.W. & Fisher, S.K. Regulation of Myo-Inositol Homeostasis in Differentiated Human NT2-N Neurons. Neurochem Res 25, 561–566 (2000). https://doi.org/10.1023/A:1007538431486

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