Persistent inflammation alters the density and distribution of voltage-activated calcium channels in subpopulations of rat cutaneous DRG neurons.
Persistent inflammation alters the density and distribution of voltage-activated calcium channels in subpopulations of rat cutaneous DRG neurons.
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DOI：
10.1016/j.pain.2010.08.030
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发表时间：
2010-12
期刊：
影响因子：
7.4
通讯作者：
Gold MS
中科院分区：
文献类型：
--
作者：
Lu SG;Zhang XL;Luo DZ;Gold MS
采用全细胞膜片钳技术、sqRT-PCR和Western blot分析，评估持续性炎症对成年大鼠皮肤DRG神经元电压激活Ca 2+通道的影响。通过皮下注射完全弗氏佐剂（CFA）诱导炎症。DiI用于鉴定支配炎症部位的DRG神经元。CFA注射后3天，高阈值Ca 2+电流（HVA）密度显着降低，在小型和中型，但不是大直径的神经元，反映了N-，L-和P/Q-型电流的减少。HVA电流的降低与编码α2γ1亚基复合物的mRNA增加有关，但N型亚基（CaV2.2）mRNA未检测到变化。在炎症部位同侧的L4和L5神经节发出的中枢神经中检测到α2γ1和CaV2.2蛋白的增加。在对来自未处理大鼠的小直径和中等直径皮肤DRG神经元进行的电流钳实验中，用Cd 2+（5 μM）阻断约40%的HT-VGCC，对皮肤DRG神经元亚群产生相反的影响（增加某些神经元的兴奋性和动作电位时程，降低其他神经元的兴奋性）。CFA注射后皮肤DRG神经元亚群中电压激活的Ca 2+通道的密度和分布的改变应有助于在炎症存在下观察到的感觉传递的变化。
The impact of persistent inflammation on voltage-activated Ca2+ channels in cutaneous DRG neurons from adult rats was assessed with whole cell patch clamp techniques, sqRT-PCR and Western blot analysis. Inflammation was induced with a subcutaneous injection of complete Freund’s adjuvant (CFA). DiI was used to identify DRG neurons innervating the site of inflammation. Three days after CFA injection, high threshold Ca2+ current (HVA) density was significantly reduced in small and medium, but not large diameter neurons, reflecting a decrease in N-, L- and P/Q-type currents. This decrease in HVA-current was associated with an increase in mRNA encoding the α2γ1-subunit complex, but no detectable change in N-type subunit (CaV2.2) mRNA. An increase in both α2γ1 and CaV2.2 protein was detected in the central nerves arising from L4 and L5 ganglia ipsilateral to the site of inflammation. In current clamp experiments on small and medium diameter cutaneous DRG neurons from naïve rats, blocking ~40% of HT-VGCC with Cd2+ (5 μM), had opposite effects on subpopulations of cutaneous DRG neurons (increasing excitability and action potential duration in some and decreasing excitability in others). The alterations in the density and distribution of voltage-activated Ca2+ channels in subpopulations of cutaneous DRG neurons that develop following CFA injection should contribute to changes in sensory transmission observed in the presence of inflammation.
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