Increased susceptibility of striatal mitochondria to calcium-induced permeability transition

Nikolai Broustovetski, Tatiana Brustovetsky, Kevin J. Purl, Michela Capano, Martin Crompton, Janet M. Dubinsky

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Mitochondria were simultaneously isolated from striatum and cortex of adult rats and compared in functional assays for their sensitivity to calcium activation of the permeability transition. Striatal mitochondria showed an increased dose-dependent sensitivity to Ca2+ compared with cortical mitochondria, as measured by mitochondrial depolarization, swelling, Ca2+ uptake, reactive oxygen species production, and respiration. Ratios of ATP to ADP were lower in striatal mitochondria exposed to calcium despite equal amounts of ADP and ATP under respiring and nonrespiring conditions. The Ca2+-induced changes were inhibited by cyclosporin A or ADP. These responses are consistent with Ca2+ activation of both low and high permeability pathways constituting the mitochondrial permeability transition. In addition to the striatal supersensitivity to induction of the permeability transition, cyclosporin A inhibition was less potent in striatal mitochondria. Immunoblots indicated that striatal mitochondria contained more cyclophilin D than cortical mitochondria. Thus striatal mitochondria may be selectively vulnerable to the permeability transition. Subsequent mitochondrial dysfunction could contribute to the initial toxicity of striatal neurons in Huntington's disease.

Original languageEnglish (US)
Pages (from-to)4858-4867
Number of pages10
JournalJournal of Neuroscience
Volume23
Issue number12
StatePublished - Jun 15 2003
Externally publishedYes

Fingerprint

Corpus Striatum
Permeability
Mitochondria
Calcium
Adenosine Diphosphate
Cyclosporine
Adenosine Triphosphate
Mitochondrial Swelling
Huntington Disease
Reactive Oxygen Species
Respiration
Neurons

Keywords

  • Brain mitochondria
  • Cyclophilin D
  • Huntington's disease
  • Neurotoxicity
  • Permeability transition
  • Regional differences

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Broustovetski, N., Brustovetsky, T., Purl, K. J., Capano, M., Crompton, M., & Dubinsky, J. M. (2003). Increased susceptibility of striatal mitochondria to calcium-induced permeability transition. Journal of Neuroscience, 23(12), 4858-4867.

Increased susceptibility of striatal mitochondria to calcium-induced permeability transition. / Broustovetski, Nikolai; Brustovetsky, Tatiana; Purl, Kevin J.; Capano, Michela; Crompton, Martin; Dubinsky, Janet M.

In: Journal of Neuroscience, Vol. 23, No. 12, 15.06.2003, p. 4858-4867.

Research output: Contribution to journalArticle

Broustovetski, N, Brustovetsky, T, Purl, KJ, Capano, M, Crompton, M & Dubinsky, JM 2003, 'Increased susceptibility of striatal mitochondria to calcium-induced permeability transition', Journal of Neuroscience, vol. 23, no. 12, pp. 4858-4867.
Broustovetski N, Brustovetsky T, Purl KJ, Capano M, Crompton M, Dubinsky JM. Increased susceptibility of striatal mitochondria to calcium-induced permeability transition. Journal of Neuroscience. 2003 Jun 15;23(12):4858-4867.
Broustovetski, Nikolai ; Brustovetsky, Tatiana ; Purl, Kevin J. ; Capano, Michela ; Crompton, Martin ; Dubinsky, Janet M. / Increased susceptibility of striatal mitochondria to calcium-induced permeability transition. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 12. pp. 4858-4867.
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