A Key Role for TRPM7 Channels in Anoxic Neuronal Death

Michelle Aarts, Koji Iihara, Wen Li Wei, Zhi Gang Xiong, Mark Arundine, Waldy Cerwinski, John F. MacDonald, Michael Tymianski

Research output: Contribution to journalArticle

567 Citations (Scopus)

Abstract

Excitotoxicity in brain ischemia triggers neuronal death and neurological disability, and yet these are not prevented by antiexcitotoxic therapy (AET) in humans. Here, we show that in neurons subjected to prolonged oxygen glucose deprivation (OGD), AET unmasks a dominant death mechanism perpetuated by a Ca2+-permeable nonselective cation conductance (IOGD). IOGD was activated by reactive oxygen/nitrogen species (ROS), and permitted neuronal Ca2+ overload and further ROS production despite AET. IOGD currents corresponded to those evoked in HEK-293 cells expressing the nonselective cation conductance TRPM7. In cortical neurons, blocking IOGD or suppressing TRPM7 expression blocked TRPM7 currents, anoxic 45Ca2+ uptake, ROS production, and anoxic death. TRPM7 suppression eliminated the need for AET to rescue anoxic neurons and permitted the survival of neurons previously destined to die from prolonged anoxia. Thus, excitotoxicity is a subset of a greater overall anoxic cell death mechanism, in which TRPM7 channels play a key role.

Original languageEnglish
Pages (from-to)863-877
Number of pages15
JournalCell
Volume115
Issue number7
DOIs
Publication statusPublished - Dec 26 2003
Externally publishedYes

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Reactive Nitrogen Species
Neurons
Oxygen
Reactive Oxygen Species
Nitrogen
Cations
HEK293 Cells
Cell death
Therapeutics
Brain Ischemia
Brain
Cell Death
Cells
Glucose

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Aarts, M., Iihara, K., Wei, W. L., Xiong, Z. G., Arundine, M., Cerwinski, W., ... Tymianski, M. (2003). A Key Role for TRPM7 Channels in Anoxic Neuronal Death. Cell, 115(7), 863-877. https://doi.org/10.1016/S0092-8674(03)01017-1

A Key Role for TRPM7 Channels in Anoxic Neuronal Death. / Aarts, Michelle; Iihara, Koji; Wei, Wen Li; Xiong, Zhi Gang; Arundine, Mark; Cerwinski, Waldy; MacDonald, John F.; Tymianski, Michael.

In: Cell, Vol. 115, No. 7, 26.12.2003, p. 863-877.

Research output: Contribution to journalArticle

Aarts, M, Iihara, K, Wei, WL, Xiong, ZG, Arundine, M, Cerwinski, W, MacDonald, JF & Tymianski, M 2003, 'A Key Role for TRPM7 Channels in Anoxic Neuronal Death', Cell, vol. 115, no. 7, pp. 863-877. https://doi.org/10.1016/S0092-8674(03)01017-1
Aarts M, Iihara K, Wei WL, Xiong ZG, Arundine M, Cerwinski W et al. A Key Role for TRPM7 Channels in Anoxic Neuronal Death. Cell. 2003 Dec 26;115(7):863-877. https://doi.org/10.1016/S0092-8674(03)01017-1
Aarts, Michelle ; Iihara, Koji ; Wei, Wen Li ; Xiong, Zhi Gang ; Arundine, Mark ; Cerwinski, Waldy ; MacDonald, John F. ; Tymianski, Michael. / A Key Role for TRPM7 Channels in Anoxic Neuronal Death. In: Cell. 2003 ; Vol. 115, No. 7. pp. 863-877.
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