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Painful nerve injury decreases sarco-endoplasmic reticulum Ca²⁺-ATPase activity in axotomized sensory neurons. Neuroscience 2013 Feb 12;231:247-57

Date

12/12/2012

Pubmed ID

23219911

Pubmed Central ID

PMC3715030

DOI

10.1016/j.neuroscience.2012.11.055

Scopus ID

2-s2.0-84872353351 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

The sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a critical pathway by which sensory neurons sequester cytosolic Ca(2+) and thereby maintain intracellular Ca(2+) homeostasis. We have previously demonstrated decreased intraluminal endoplasmic reticulum Ca(2+) concentration in traumatized sensory neurons. Here we examine SERCA function in dissociated sensory neurons using Fura-2 fluorometry. Blocking SERCA with thapsigargin (1 μM) increased resting [Ca(2+)](c) and prolonged recovery (τ) from transients induced by neuronal activation (elevated bath K(+)), demonstrating SERCA contributes to control of resting [Ca(2+)](c) and recovery from transient [Ca(2+)](c) elevation. To evaluate SERCA in isolation, plasma membrane Ca(2+) ATPase was blocked with pH 8.8 bath solution and mitochondrial buffering was avoided by keeping transients small (≤ 400 nM). Neurons axotomized by spinal nerve ligation (SNL) showed a slowed rate of transient recovery compared to control neurons, representing diminished SERCA function, whereas neighboring non-axotomized neurons from SNL animals were unaffected. Injury did not affect SERCA function in large neurons. Repeated depolarization prolonged transient recovery, showing that neuronal activation inhibits SERCA function. These findings suggest that injury-induced loss of SERCA function in small sensory neurons may contribute to the generation of pain following peripheral nerve injury.

Author List

Duncan C, Mueller S, Simon E, Renger JJ, Uebele VN, Hogan QH, Wu HE

Author

Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Axotomy
Calcium
Calcium Signaling
Endoplasmic Reticulum
Enzyme Inhibitors
Male
Pain
Rats
Rats, Sprague-Dawley
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Sensory Receptor Cells
Spinal Nerves
Thapsigargin