Store-operated Ca2+ entry in sensory neurons: functional role and the effect of painful nerve injury. J Neurosci 2011 Mar 09;31(10):3536-49
Date
03/11/2011Pubmed ID
21389210Pubmed Central ID
PMC3565463DOI
10.1523/JNEUROSCI.5053-10.2011Scopus ID
2-s2.0-79952394104 (requires institutional sign-in at Scopus site) 86 CitationsAbstract
Painful nerve injury disrupts levels of cytoplasmic and stored Ca(2+) in sensory neurons. Since influx of Ca(2+) may occur through store-operated Ca(2+) entry (SOCE) as well as voltage- and ligand-activated pathways, we sought confirmation of SOCE in sensory neurons from adult rats and examined whether dysfunction of SOCE is a possible pathogenic mechanism. Dorsal root ganglion neurons displayed a fall in resting cytoplasmic Ca(2+) concentration when bath Ca(2+) was withdrawn, and a subsequent elevation of cytoplasmic Ca(2+) concentration (40 ± 5 nm) when Ca(2+) was reintroduced, which was amplified by store depletion with thapsigargin (1 μm), and was significantly reduced by blockers of SOCE, but was unaffected by antagonists of voltage-gated membrane Ca(2+) channels. We identified the underlying inwardly rectifying Ca(2+)-dependent I(CRAC) (Ca(2+) release activated current), as well as a large thapsigargin-sensitive inward current activated by withdrawal of bath divalent cations, representing SOCE. Molecular components of SOCE, specifically STIM1 and Orai1, were confirmed in sensory neurons at both the transcript and protein levels. Axonal injury by spinal nerve ligation (SNL) elevated SOCE and I(CRAC). However, SOCE was comparable in injured and control neurons when stores were maximally depleted by thapsigargin, and STIM1 and Orai1 levels were not altered by SNL, showing that upregulation of SOCE after SNL is driven by store depletion. Blockade of SOCE increased neuronal excitability in control and injured neurons, whereas injured neurons showed particular dependence on SOCE for maintaining levels of cytoplasmic and stored Ca(2+), which indicates a compensatory role for SOCE after injury.
Author List
Gemes G, Bangaru ML, Wu HE, Tang Q, Weihrauch D, Koopmeiners AS, Cruikshank JM, Kwok WM, Hogan QHAuthors
Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of WisconsinWai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin
Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Blotting, Western
Calcium
Calcium Channels
Calcium Signaling
Cells, Cultured
Ganglia, Spinal
Hyperalgesia
Immunohistochemistry
Male
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Sensory Receptor Cells
Spinal Nerves
