Mitochondrial Ca 2+ uptake is essential for synaptic plasticity in pain

Hee Young Kim, Kwan Yeop Lee, Ying Lu, Jigong Wang, Lian Cui, Sangjeong Kim, Jin Mo Chung, Kyungsoon Chung

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

The increase of cytosolic free Ca 2+ ([Ca 2+ ] c ) due to NMDA receptor activation is a key step for spinal cord synaptic plasticity by altering cellular signal transduction pathways. We focus on this plasticity as a cause of persistent pain. To provide a mechanism for these classic findings, we report that [Ca 2+ ] c does not trigger synaptic plasticity directly but must first enter into mitochondria. Interfering with mitochondrial Ca 2+ uptake during a [Ca 2+ ] c increase blocks induction of behavioral hyperalgesia and accompanying downstream cell signaling, with reduction of spinal long-term potentiation (LTP). Furthermore, reducing the accompanying mitochondrial superoxide levels lessens hyperalgesia and LTP induction. These results indicate that [Ca 2+ ] c requires downstream mitochondrial Ca 2+ uptake with consequent production of reactive oxygen species (ROS) for synaptic plasticity underlying chronic pain. These results suggest modifying mitochondrial Ca 2+ uptake and thus ROS as a type of chronic pain therapy that should also have broader biologic significance.

Original languageEnglish
Pages (from-to)12982-12991
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number36
DOIs
StatePublished - 7 Sep 2011

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Neuronal Plasticity
Long-Term Potentiation
Hyperalgesia
Pain
Chronic Pain
Reactive Oxygen Species
N-Methyl-D-Aspartate Receptors
Superoxides
Signal Transduction
Spinal Cord
Mitochondria
Therapeutics

Cite this

Kim, Hee Young ; Lee, Kwan Yeop ; Lu, Ying ; Wang, Jigong ; Cui, Lian ; Kim, Sangjeong ; Chung, Jin Mo ; Chung, Kyungsoon. / Mitochondrial Ca 2+ uptake is essential for synaptic plasticity in pain In: Journal of Neuroscience. 2011 ; Vol. 31, No. 36. pp. 12982-12991.
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abstract = "The increase of cytosolic free Ca 2+ ([Ca 2+ ] c ) due to NMDA receptor activation is a key step for spinal cord synaptic plasticity by altering cellular signal transduction pathways. We focus on this plasticity as a cause of persistent pain. To provide a mechanism for these classic findings, we report that [Ca 2+ ] c does not trigger synaptic plasticity directly but must first enter into mitochondria. Interfering with mitochondrial Ca 2+ uptake during a [Ca 2+ ] c increase blocks induction of behavioral hyperalgesia and accompanying downstream cell signaling, with reduction of spinal long-term potentiation (LTP). Furthermore, reducing the accompanying mitochondrial superoxide levels lessens hyperalgesia and LTP induction. These results indicate that [Ca 2+ ] c requires downstream mitochondrial Ca 2+ uptake with consequent production of reactive oxygen species (ROS) for synaptic plasticity underlying chronic pain. These results suggest modifying mitochondrial Ca 2+ uptake and thus ROS as a type of chronic pain therapy that should also have broader biologic significance.",
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Kim, HY, Lee, KY, Lu, Y, Wang, J, Cui, L, Kim, S, Chung, JM & Chung, K 2011, ' Mitochondrial Ca 2+ uptake is essential for synaptic plasticity in pain ', Journal of Neuroscience, vol. 31, no. 36, pp. 12982-12991. https://doi.org/10.1523/JNEUROSCI.3093-11.2011

Mitochondrial Ca 2+ uptake is essential for synaptic plasticity in pain . / Kim, Hee Young; Lee, Kwan Yeop; Lu, Ying; Wang, Jigong; Cui, Lian; Kim, Sangjeong; Chung, Jin Mo; Chung, Kyungsoon.

In: Journal of Neuroscience, Vol. 31, No. 36, 07.09.2011, p. 12982-12991.

Research output: Contribution to journalArticleResearchpeer-review

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