Mitochondrial Ca2+ uptake is essential for synaptic plasticity in pain

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

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The increase of cytosolic free Ca2+([Ca2+]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 [Ca2+]c does not trigger synaptic plasticity directly but must first enter into mitochondria. Interfering with mitochondrial Ca2+ uptake during a [Ca2+]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 [Ca2+]c requires downstream mitochondrial Ca2+uptake with consequent production of reactive oxygen species (ROS) for synaptic plasticity underlying chronic pain. These results suggest modifying mitochondrial Ca2+ uptake and thus ROS as a type of chronic pain therapy that should also have broader biologic significance.

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kim, H. Y., Lee, K. Y., Lu, Y., Wang, J., Cui, L., Kim, S. J., ... Chung, K. (2011). Mitochondrial Ca2+ uptake is essential for synaptic plasticity in pain. Journal of Neuroscience, 31(36), 12982-12991. https://doi.org/10.1523/JNEUROSCI.3093-11.2011

Mitochondrial Ca2+ uptake is essential for synaptic plasticity in pain. / Kim, Hee Young; Lee, Kwan Yeop; Lu, Ying; Wang, Jigong; Cui, Lian; Kim, Sang Jeong; Chung, Jin; Chung, Kyungsoon.

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

Research output: Contribution to journalArticle

Kim, HY, Lee, KY, Lu, Y, Wang, J, Cui, L, Kim, SJ, Chung, J & Chung, K 2011, 'Mitochondrial Ca2+ 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
Kim, Hee Young ; Lee, Kwan Yeop ; Lu, Ying ; Wang, Jigong ; Cui, Lian ; Kim, Sang Jeong ; Chung, Jin ; Chung, Kyungsoon. / Mitochondrial Ca2+ uptake is essential for synaptic plasticity in pain. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 36. pp. 12982-12991.
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