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NMDA-induced calcium loads recycle across the mitochondrial inner membrane of hippocampal neurons in culture.
J Neurophysiol. 2002 Feb; 87(2):740-9.JN

Abstract

Mitochondria sequester N-methyl-D-aspartate (NMDA)-induced Ca(2+) loads and regulate the shape of intracellular Ca(2+) concentration ([Ca(2+)](i)) responses in neurons. When isolated mitochondria are exposed to high [Ca(2+)](,) Ca(2+) enters the matrix via the uniporter and returns to the cytosol by Na(+)/Ca(2+) exchange. Released Ca(2+) may re-enter the mitochondrion recycling across the inner membrane dissipating respiratory energy. Ca(2+) recycling, the continuous uptake and release of Ca(2+) by mitochondria, has not been described in intact neurons. Here we used single-cell microfluorimetry to measure [Ca(2+)](i) and mitochondrially targeted aequorin to measure matrix Ca(2+) concentration ([Ca(2+)](mt)) to determine whether Ca(2+) recycles across the mitochondrial inner membrane in intact neurons following treatment with NMDA. We used ruthenium red and CGP 37157 to block uptake via the uniporter and release via Na(+)/Ca(2+) exchange, respectively. As predicted by the Ca(2+) recycling hypothesis, blocking the uniporter immediately following challenge with 200 microM NMDA produced a rapid and transient increase in cytosolic Ca(2+) without a corresponding increase in matrix Ca(2+). Blocking mitochondrial Ca(2+) release produced the opposite effect, depressing cytosolic Ca(2+) levels and prolonging the time for matrix Ca(2+) levels to recover. The Ca(2+) recycling hypothesis uniquely predicts these reciprocal changes in the Ca(2+) levels between the two compartments. Ca(2+) recycling was not detected following treatment with 20 microM NMDA. Thus Ca(2+) recycling across the inner membrane was more pronounced following treatment with a high relative to a low concentration of NMDA, consistent with a role in Ca(2+)-dependent neurotoxicity.

Authors+Show Affiliations

Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455-0217, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11826043

Citation

Wang, Guang Jian, and Stanley A. Thayer. "NMDA-induced Calcium Loads Recycle Across the Mitochondrial Inner Membrane of Hippocampal Neurons in Culture." Journal of Neurophysiology, vol. 87, no. 2, 2002, pp. 740-9.
Wang GJ, Thayer SA. NMDA-induced calcium loads recycle across the mitochondrial inner membrane of hippocampal neurons in culture. J Neurophysiol. 2002;87(2):740-9.
Wang, G. J., & Thayer, S. A. (2002). NMDA-induced calcium loads recycle across the mitochondrial inner membrane of hippocampal neurons in culture. Journal of Neurophysiology, 87(2), 740-9.
Wang GJ, Thayer SA. NMDA-induced Calcium Loads Recycle Across the Mitochondrial Inner Membrane of Hippocampal Neurons in Culture. J Neurophysiol. 2002;87(2):740-9. PubMed PMID: 11826043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA-induced calcium loads recycle across the mitochondrial inner membrane of hippocampal neurons in culture. AU - Wang,Guang Jian, AU - Thayer,Stanley A, PY - 2002/2/5/pubmed PY - 2002/3/27/medline PY - 2002/2/5/entrez SP - 740 EP - 9 JF - Journal of neurophysiology JO - J Neurophysiol VL - 87 IS - 2 N2 - Mitochondria sequester N-methyl-D-aspartate (NMDA)-induced Ca(2+) loads and regulate the shape of intracellular Ca(2+) concentration ([Ca(2+)](i)) responses in neurons. When isolated mitochondria are exposed to high [Ca(2+)](,) Ca(2+) enters the matrix via the uniporter and returns to the cytosol by Na(+)/Ca(2+) exchange. Released Ca(2+) may re-enter the mitochondrion recycling across the inner membrane dissipating respiratory energy. Ca(2+) recycling, the continuous uptake and release of Ca(2+) by mitochondria, has not been described in intact neurons. Here we used single-cell microfluorimetry to measure [Ca(2+)](i) and mitochondrially targeted aequorin to measure matrix Ca(2+) concentration ([Ca(2+)](mt)) to determine whether Ca(2+) recycles across the mitochondrial inner membrane in intact neurons following treatment with NMDA. We used ruthenium red and CGP 37157 to block uptake via the uniporter and release via Na(+)/Ca(2+) exchange, respectively. As predicted by the Ca(2+) recycling hypothesis, blocking the uniporter immediately following challenge with 200 microM NMDA produced a rapid and transient increase in cytosolic Ca(2+) without a corresponding increase in matrix Ca(2+). Blocking mitochondrial Ca(2+) release produced the opposite effect, depressing cytosolic Ca(2+) levels and prolonging the time for matrix Ca(2+) levels to recover. The Ca(2+) recycling hypothesis uniquely predicts these reciprocal changes in the Ca(2+) levels between the two compartments. Ca(2+) recycling was not detected following treatment with 20 microM NMDA. Thus Ca(2+) recycling across the inner membrane was more pronounced following treatment with a high relative to a low concentration of NMDA, consistent with a role in Ca(2+)-dependent neurotoxicity. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/11826043/NMDA_induced_calcium_loads_recycle_across_the_mitochondrial_inner_membrane_of_hippocampal_neurons_in_culture_ L2 - https://journals.physiology.org/doi/10.1152/jn.00345.2001?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -