钙内流的恢复可纠正损伤大鼠背根神经节神经元的膜兴奋性过高。
Restoration of calcium influx corrects membrane hyperexcitability in injured rat dorsal root ganglion neurons.
作者信息
Hogan Quinn, Lirk Philipp, Poroli Mark, Rigaud Marcel, Fuchs Andreas, Fillip Patrick, Ljubkovic Marko, Gemes Geza, Sapunar Damir
机构信息
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
出版信息
Anesth Analg. 2008 Sep;107(3):1045-51. doi: 10.1213/ane.0b013e31817bd1f0.
BACKGROUND
We have previously shown that a decrease of inward Ca(2+) flux (I(Ca)) across the sensory neuron plasmalemma, such as happens after axotomy, increases neuronal excitability. From this, we predicted that increasing I(Ca) in injured neurons should correct their hyperexcitability.
METHODS
The influence of increased or decreased I(Ca) upon membrane biophysical variables and excitability was determined during recording from A-type neurons in nondissociated dorsal root ganglia after spinal nerve ligation using an intracellular recording technique.
RESULTS
When the bath Ca(2+) level was increased to promote I(Ca), the after-hyperpolarization was decreased and repetitive firing was suppressed, which also followed amplification of Ca(2+)-activated K(+) current with selective agents NS1619 and NS309. A decreased external bath Ca(2+) concentration had the opposite effects, similar to previous observations in uninjured neurons.
CONCLUSIONS
These findings indicate that at least a part of the hyperexcitability of somatic sensory neurons after axotomy is attributable to diminished inward Ca(2+) flux, and that measures to restore I(Ca) may potentially be therapeutic for painful peripheral neuropathy.
背景
我们之前已经表明，跨感觉神经元质膜的内向Ca(2+)通量（I(Ca)）降低，如轴突切断后发生的情况，会增加神经元兴奋性。据此，我们预测增加受损神经元中的I(Ca)应能纠正其过度兴奋性。
方法
使用细胞内记录技术，在脊髓神经结扎后的非解离背根神经节中的A型神经元记录过程中，确定I(Ca)增加或减少对膜生物物理变量和兴奋性的影响。
结果
当浴液Ca(2+)水平升高以促进I(Ca)时，后超极化降低且重复放电受到抑制，这也伴随着用选择性药物NS1619和NS309对Ca(2+)激活的K(+)电流的放大。降低外部浴液Ca(2+)浓度则产生相反的效果，这与之前在未受损神经元中的观察结果相似。
结论
这些发现表明，轴突切断后躯体感觉神经元过度兴奋性的至少一部分可归因于内向Ca(2+)通量减少，并且恢复I(Ca)的措施可能对疼痛性周围神经病变具有潜在的治疗作用。
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