title: 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.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 W Watertown Plank, Milwaukee, WI 53226, USA; Zablocki VA Medical Center, 5000 W National Avenue, Milwaukee, WI 53295, USA.
authors.forename: Quinn H
authors.initials: QH
authors.lastname: Hogan
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 W Watertown Plank, Milwaukee, WI 53226, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Sprick
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 W Watertown Plank, Milwaukee, WI 53226, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 W Watertown Plank, Milwaukee, WI 53226, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Mueller
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 W Watertown Plank, Milwaukee, WI 53226, USA; Department of Pharmacology and Toxicology, Medical College of Wisconsin, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Bienengraeber
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 W Watertown Plank, Milwaukee, WI 53226, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 W Watertown Plank, Milwaukee, WI 53226, USA. Electronic address: hwu@mcw.edu.
authors.forename: Hsiang-En
authors.initials: HE
authors.lastname: Wu
mesh_terms: D000818:Animals; D019771:Axotomy; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000293:injuries* / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D009840:Oligomycins; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002118:Calcium
keywords: Mitochondrial Ca(2+); Neuropathic pain; Sensory neuron function; Spinal nerve ligation