Divergent effects of painful nerve injury on mitochondrial Ca2+ buffering in axotomized and adjacent sensory neurons

Quinn H. Hogan, Chelsea Sprick, Yuan Guo, Samantha Mueller, Martin Bienengraeber, Bin Pan, Hsiang En Wu

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Mitochondria critically regulate cytoplasmic Ca2+ concentration ([Ca2+]c), but the effects of sensory neuron injury have not been examined. Using FCCP (1 μM) to eliminate mitochondrial Ca2+ uptake combined with oligomycin (10 μM) to prevent ATP depletion, we first identified features of depolarization-induced neuronal [Ca2+]c transients that are sensitive to blockade of mitochondrial Ca2+ buffering in order to assess mitochondrial contributions to [Ca2+]c regulation. This established the loss of a shoulder during the recovery of the depolarization (K+)-induced transient, increased transient peak and area, and elevated shoulder level as evidence of diminished mitochondrial Ca2+ buffering. We then examined transients in Control neurons and neurons from the 4th lumbar (L4) and 5th lumbar (L5) dorsal root ganglia after L5 spinal nerve ligation (SNL). The SNL L4 neurons showed decreased transient peak and area compared to control neurons, while the SNL L5 neurons showed increased shoulder level. Additionally, SNL L4 neurons developed shoulders following transients with lower peaks than Control neurons. Application of FCCP plus oligomycin elevated resting [Ca2+]c in SNL L4 neurons more than in Control neurons. Whereas application of FCCP plus oligomycin 2 s after neuronal depolarization initiated mitochondrial Ca2+ release in most Control and SNL L4 neurons, this usually failed to release mitochondrial Ca2+ from SNL L5 neurons. For comparable cytoplasmic Ca2+ loads, the releasable mitochondrial Ca2+ in SNL L5 neurons was less than Control while it was increased in SNL L4 neurons. These findings show diminished mitochondrial Ca2+ buffering in axotomized SNL L5 neurons but enhanced Ca2+ buffering by neurons in adjacent SNL L4 neurons.

Original languageEnglish (US)
Pages (from-to)112-125
Number of pages14
JournalBrain Research
StatePublished - Nov 17 2014
Externally publishedYes


  • Mitochondrial Ca
  • Neuropathic pain
  • Sensory neuronfunction
  • Spinal nerveligation

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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