Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Gemes, G; Rigaud, M; Weyker, PD; Abram, SE; Weihrauch, D; Poroli, M; Zoga, V; Hogan, QH.
Depletion of calcium stores in injured sensory neurons: anatomic and functional correlates.
Anesthesiology. 2009; 111(2): 393-405.
Doi: 10.1097/ALN.0b013e3181ae63b0
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- Führende Autor*innen der Med Uni Graz
- Gemes Geza
- Co-Autor*innen der Med Uni Graz
- Rigaud Marcel
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- Abstract:
- Background: Painful nerve injury leads to disrupted Ca2+ signaling in primary sensory neurons, including decreased endoplasmic reticulum (ER) Ca2+ storage. This study examines potential causes and functional consequences of Ca2+ store limitation after injury. Methods: Neurons were dissociated from axotomized ftfth lumbar (L5) and the adjacent L4 dorsal root ganglia after L5 spinal nerve ligation that produced hyperalgesia, and they were compared to neurons from control animals. intracellular Ca2+ levels were measured with Fura-2 microfluorometry, and ER was labeled with probes or antibodies. Ultrastructural morphology was analyzed by electron microscopy of nondissociated dorsal root ganglia, and intracellular electrophysiological recordings were obtained from intact ganglia. Results: Live neuron staining with BODIPY FL-X thapsigargin (Invitrogen, Carlsbad, CA) revealed a 40% decrease in sarco-endoplasmic reticulum Ca2+-ATPase binding in axotomized L5 neurons and a 34% decrease in L4 neurons. Immunocytochemical labeling for the ER Ca2+-binding protein calreticulin was unaffected by injury. Total length of ER profiles In electron micrographs was reduced by 53% in small axotomized L5 neurons, but it was increased in L4 neurons. Cisternal stacks of ER and aggregation of ribosomes occurred less frequently in axotomized. neurons. Ca2+-induced Ca2+ release, examined by microfluorometry with dantrolene, was eliminated in axotomized neurons. Pharmacologic blockade of Ca2+-induced Ca2+ release with dantrolene produced hypcrexcitability in control neurons, confirming its functional importance. Conclusions: After axotomy, ER Ca2+ stores are reduced by anatomic loss and possibly diminished sarco-endoplasmic reticulum Ca2+-ATPase. The resulting disruption of Ca2+-induced Ca2+ release and protein synthesis may contribute to the generation of neuropathic pain.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Boron Compounds -
- Calcium - metabolism
- Calcium Signaling - drug effects
- Calcium-Binding Protein, Vitamin D-Dependent - metabolism
- Cytoplasm - drug effects
- Dantrolene - pharmacology
- Electrophysiology -
- Endoplasmic Reticulum - drug effects
- Fluorescent Dyes -
- Hyperalgesia - pathology
- Immunohistochemistry -
- Ligation -
- Male -
- Microscopy, Electron -
- Pain Measurement - drug effects
- Rats -
- Rats, Sprague-Dawley -
- Sensory Receptor Cells - drug effects
- Spinal Nerves - drug effects