Expression of background potassium channels in rat DRG is cell-specific and down-regulated in a neuropathic pain model.
Expression of background potassium channels in rat DRG is cell-specific and down-regulated in a neuropathic pain model.
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DOI：
10.1016/j.mcn.2013.08.002
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Martina M
中科院分区：
文献类型：
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作者：
Pollema-Mays SL;Centeno MV;Ashford CJ;Apkarian AV;Martina M
神经病理性疼痛与DRG神经元的过度兴奋有关。尽管渗漏钾通道对于神经元兴奋性的重要性，但是关于它们在DRG中的细胞特异性表达以及在神经病理性疼痛中的可能调节知之甚少。在DRG神经元中表达多种渗漏通道，包括TASK 1、TASK 3、TRESK、TRAAK、TWIK 1、TREK 1和TREK 2，但它们在不同细胞类型中的分布知之甚少。我们的免疫组织化学研究显示，TWIK 1在大中型神经元中表达强劲，与TRPV 1或IB 4染色无重叠。相反，TASK 1和TASK 3选择性地在小细胞中表达; TASK 1表达与TRPV 1阳性细胞紧密重叠，而TASK 3在TRPV 1和IB 4阴性细胞中表达。我们还研究了这些通道的mRNA表达在L4-L5 DRG在对照条件下和长达4周后备用神经损伤病变。我们发现TWIK 1的表达比TASK 1和TASK 3高得多，并且在神经性损伤后1、2和4周强烈降低。另一方面，TASK 3表达在手术后1周降低，但在2周时恢复至基线; TASK 1在任何时间点均未显示显著变化。这些数据表明TWIK 1参与维持疼痛状况。
Neuropathic pain is associated with hyperexcitability of DRG neurons. Despite the importance of leakage potassium channels for neuronal excitability, little is known about their cell-specific expression in DRGs and possible modulation in neuropathic pain. Multiple leakage channels are expressed in DRG neurons, including TASK1, TASK3, TRESK, TRAAK, TWIK1, TREK1 and TREK2 but little is known about their distribution among different cell types. Our immunohistochemical studies show robust TWIK1 expression in large and medium size neurons, without overlap with TRPV1 or IB4 staining. TASK1 and TASK3, on the contrary, are selectively expressed in small cells; TASK1 expression closely overlaps TRPV1-positive cells, while TASK3 is expressed in TRPV1- and IB4-negative cells. We also studied mRNA expression of these channels in L4-L5 DRGs in control conditions and up to 4 weeks after spared nerve injury lesion. We found that TWIK1 expression is much higher than TASK1 and TASK3 and is strongly decreased 1, 2 and 4 weeks after neuropathic injury. TASK3 expression, on the other hand, decreases 1 week after surgery but reverts to baseline by 2 weeks; TASK1 shows no significant change at any time point. These data suggest an involvement of TWIK1 in the maintenance of the pain condition.