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Divergent effects of painful nerve injury on mitochondrial Ca(2+) buffering in axotomized and adjacent sensory neurons.

Abstract：

:Mitochondria critically regulate cytoplasmic Ca(2+) concentration ([Ca(2+)]c), but the effects of sensory neuron injury have not been examined. Using FCCP (1µM) to eliminate mitochondrial Ca(2+) uptake combined with oligomycin (10µM) to prevent ATP depletion, we first identified features of depolarization-induced neuronal [Ca(2+)]c transients that are sensitive to blockade of mitochondrial Ca(2+) buffering in order to assess mitochondrial contributions to [Ca(2+)]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 Ca(2+) 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 [Ca(2+)]c in SNL L4 neurons more than in Control neurons. Whereas application of FCCP plus oligomycin 2s after neuronal depolarization initiated mitochondrial Ca(2+) release in most Control and SNL L4 neurons, this usually failed to release mitochondrial Ca(2+) from SNL L5 neurons. For comparable cytoplasmic Ca(2+) loads, the releasable mitochondrial Ca(2+) in SNL L5 neurons was less than Control while it was increased in SNL L4 neurons. These findings show diminished mitochondrial Ca(2+) buffering in axotomized SNL L5 neurons but enhanced Ca(2+) buffering by neurons in adjacent SNL L4 neurons.

journal_name

Brain Res

journal_title

Brain research

authors

Hogan QH,Sprick C,Guo Y,Mueller S,Bienengraeber M,Pan B,Wu HE

doi

10.1016/j.brainres.2014.09.040

subject

Has Abstract

pub_date

2014-11-17 00:00:00

pages

112-25

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(14)01262-1

journal_volume

1589

pub_type

杂志文章

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Divergent effects of painful nerve injury on mitochondrial Ca(2+) buffering in axotomized and adjacent sensory neurons.