Painful nerve injury decreases sarco-endoplasmic reticulum Ca²⁺-ATPase activity in axotomized sensory neurons.
Painful nerve injury decreases sarco-endoplasmic reticulum Ca²⁺-ATPase activity in axotomized sensory neurons.
复制标题
DOI：
10.1016/j.neuroscience.2012.11.055
复制
发表时间：
2013-02-12
期刊：
影响因子：
3.3
通讯作者：
Wu HE
中科院分区：
文献类型：
--
作者：
Duncan C;Mueller S;Simon E;Renger JJ;Uebele VN;Hogan QH;Wu HE
肌质内质网Ca ~（2+）-ATP酶（SERCA）是感觉神经元螯合胞浆Ca ~（2+）从而维持胞内Ca ~（2+）稳态的重要途径。我们以前已经证明了减少管腔内内质网Ca 2+浓度在创伤的感觉神经元。在这里，我们研究SERCA功能分离的感觉神经元使用Fura-2荧光。用毒胡萝卜素（1 μM）阻断SERCA可增加静息[Ca 2 +]c和延长神经元激活（升高的浴K+）诱导的瞬变恢复（τ），表明SERCA有助于控制静息[Ca 2 +]c和从瞬时[Ca 2 +]c升高恢复。为了评价分离的SERCA，用pH 8.8的浴溶液阻断质膜Ca 2 + ATP酶，并通过保持小的瞬变（≤400 nM）来避免线粒体缓冲。与对照神经元相比，通过脊神经结扎（SNL）进行轴突切断的神经元显示出缓慢的瞬时恢复速率，这表示SERCA功能减弱，而来自SNL动物的邻近非轴突切断的神经元不受影响。损伤不影响大神经元的SERCA功能。重复去极化延长短暂恢复，表明神经元激活抑制SERCA功能。这些发现表明，损伤引起的SERCA功能的损失，在小的感觉神经元可能有助于产生疼痛周围神经损伤后。
The sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) is a critical pathway by which sensory neurons sequester cytosolic Ca2+ and thereby maintain intracellular Ca2+ homeostasis. We have previously demonstrated decreased intraluminal endoplasmic reticulum Ca2+ 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 [Ca2+]c and prolonged recovery (τ) from transients induced by neuronal activation (elevated bath K+), demonstrating SERCA contributes to control of resting [Ca2+]c and recovery from transient [Ca2+]c elevation. To evaluate SERCA in isolation, plasma membrane Ca2+ 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.
登录
查看更多内容
DOI：
10.1523/jneurosci.5053-10.2011
发表时间：
2011-03-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gemes G;Bangaru ML;Wu HE;Tang Q;Weihrauch D;Koopmeiners AS;Cruikshank JM;Kwok WM;Hogan QH
通讯作者：
Hogan QH
影响因子：
5.5
作者：
FRIEL, DD;TSIEN, RW
通讯作者：
TSIEN, RW
影响因子：
4.1
作者：
Gallego-Sandin, Sonia;Teresa Alonso, Maria;Garcia-Sancho, Javier
通讯作者：
Garcia-Sancho, Javier
影响因子：
4
作者：
Gover, Tony D.;Moreira, Thais H. V.;Weinreich, Daniel
通讯作者：
Weinreich, Daniel
影响因子：
5.5
作者：
BENHAM, CD;EVANS, ML;MCBAIN, CJ
通讯作者：
MCBAIN, CJ