Inflammation-induced changes in BK(Ca) currents in cutaneous dorsal root ganglion neurons from the adult rat.
Inflammation-induced changes in BK(Ca) currents in cutaneous dorsal root ganglion neurons from the adult rat.
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DOI：
10.1186/1744-8069-8-37
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发表时间：
2012-07-04
期刊：
影响因子：
3.3
通讯作者：
Gold MS
中科院分区：
文献类型：
--
作者：
Zhang XL;Mok LP;Lee KY;Charbonnet M;Gold MS
炎症引起的初级传入神经敏化与 K+ 电流的减少有关。然而，K+电流的类型和减少的基础根据神经支配的目标而变化。由于大鼠后爪的无毛皮肤经常用于评估持续性疼痛模型中伤害感受的变化，因此本研究的目的是确定 K+ 电流对炎症诱导的皮肤传入敏化的类型和程度。采用全细胞和穿孔贴片技术对来自幼稚和发炎（完成弗氏佐剂注射后 3 天）大鼠的急性分离逆行标记皮肤背根神经节神经元进行研究。炎症诱导的小直径皮肤神经元的敏化与动作电位持续时间的增加和后超极化的衰减率相关。然而，未检测到电压门控 K+ 电流的变化。相比之下，小直径 IB4+ 神经元中 Ca2+ 调节的伊贝里奥毒素敏感和桩线敏感 K+ (BKCa) 电流显着较小。电流的降低与 BKCa 通道 α 或 β 亚基总蛋白水平的可检测变化无关。单细胞 PCR 分析揭示了 α 亚基剪接变体和 β 亚基表达模式的显着变化，这与炎症诱导的皮肤神经元 BKCa 电流生物物理特性的变化至少部分一致。这项研究的结果为以下结论提供了额外的支持：选择性治疗特定身体区域产生的疼痛，即使没有必要，也是可能的。由于 BKCa 电流的减少似乎有助于炎症诱导的皮肤传入敏感化，因此 BKCa 通道开放剂可能对治疗炎性疼痛有效。
Inflammation-induced sensitization of primary afferents is associated with a decrease in K+ current. However, the type of K+ current and basis for the decrease varies as a function of target of innervation. Because glabrous skin of the rat hindpaw is used often to assess changes in nociception in models of persistent pain, the purpose of the present study was to determine the type and extent to which K+ currents contribute to the inflammation-induced sensitization of cutaneous afferents. Acutely dissociated retrogradely labeled cutaneous dorsal root ganglion neurons from naïve and inflamed (3 days post complete Freund’s adjuvant injection) rats were studied with whole cell and perforated patch techniques. Inflammation-induced sensitization of small diameter cutaneous neurons was associated with an increase in action potential duration and rate of decay of the afterhyperpolarization. However, no changes in voltage-gated K+ currents were detected. In contrast, Ca2+ modulated iberiotoxin sensitive and paxilline sensitive K+ (BKCa) currents were significantly smaller in small diameter IB4+ neurons. This decrease in current was not associated with a detectable change in total protein levels of the BKCa channel α or β subunits. Single cell PCR analysis revealed a significant change in the pattern of expression of α subunit splice variants and β subunits that were consistent, at least in part, with inflammation-induced changes in the biophysical properties of BKCa currents in cutaneous neurons. Results of this study provide additional support for the conclusion that it may be possible, if not necessary to selectively treat pain arising from specific body regions. Because a decrease in BKCa current appears to contribute to the inflammation-induced sensitization of cutaneous afferents, BKCa channel openers may be effective for the treatment of inflammatory pain.
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影响因子：
3.3
作者：
Djouhri, L;Lawson, SN
通讯作者：
Lawson, SN
影响因子：
5.5
作者：
Scholz, A;Gruss, M;Vogel, W
通讯作者：
Vogel, W
影响因子：
5.3
作者：
Hu, H;Shao, LR;Storm, JF
通讯作者：
Storm, JF
影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW
BKCa 电流在成年大鼠皮肤伤害性背根神经节神经元亚群中丰富。
DOI：
10.1111/j.1460-9568.2009.07060.x
发表时间：
2010-02
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Zhang XL;Mok LP;Katz EJ;Gold MS
通讯作者：
Gold MS