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Plasma membrane poration by opioid neuropeptides: a possible mechanism of pathological signal transduction
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2015 (English)In: Cell Death and Disease, ISSN 2041-4889, Vol. 6, e1683Article in journal (Refereed) Published
Abstract [en]

Neuropeptides induce signal transduction across the plasma membrane by acting through cell-surface receptors. The dynorphins, endogenous ligands for opioid receptors, are an exception; they also produce non-receptor-mediated effects causing pain and neurodegeneration. To understand non-receptor mechanism(s), we examined interactions of dynorphins with plasma membrane. Using fluorescence correlation spectroscopy and patch-clamp electrophysiology, we demonstrate that dynorphins accumulate in the membrane and induce a continuum of transient increases in ionic conductance. This phenomenon is consistent with stochastic formation of giant (similar to 2.7 nm estimated diameter) unstructured non-ion-selective membrane pores. The potency of dynorphins to porate the plasma membrane correlates with their pathogenic effects in cellular and animal models. Membrane poration by dynorphins may represent a mechanism of pathological signal transduction. Persistent neuronal excitation by this mechanism may lead to profound neuropathological alterations, including neurodegeneration and cell death.

Place, publisher, year, edition, pages
2015. Vol. 6, e1683
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
URN: urn:nbn:se:uu:diva-255310DOI: 10.1038/cddis.2015.39ISI: 000353723300017PubMedID: 25766322OAI: oai:DiVA.org:uu-255310DiVA: diva2:822420
Available from: 2015-06-16 Created: 2015-06-15 Last updated: 2015-06-16Bibliographically approved

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Bazov, IgorBakalkin, Georgy
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Department of Pharmaceutical Biosciences
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Cell Death and Disease
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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