Neurokinins inhibit low threshold inactivating K+ currents in capsaicin responsive DRG neurons.
Neurokinins inhibit low threshold inactivating K+ currents in capsaicin responsive DRG neurons.
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DOI：
10.1016/j.expneurol.2009.07.016
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发表时间：
2009-10
影响因子：
5.3
通讯作者：
de Groat, William C.
中科院分区：
文献类型：
--
作者：
Sculptoreanu, Adrian;Artim, Debra E.;de Groat, William C.
从背根神经节(DRG)神经元末梢释放的神经激肽(NK)可能通过一种自我反馈机制控制这些神经元的放电。在这项研究中，我们使用膜片钳记录技术来确定NKs是否通过调制K+电流来改变大鼠L4-S3背根节神经元的兴奋性。在辣椒素(CAPS)反应相神经元中，P物质(SP)降低动作电位(AP)阈值，增加去极化电流脉冲诱发的AP数目。SP和选择性NK2激动剂[β-Ala8]-Neurokinin A(4-10)也可抑制低阈值失活K+电流，这种低阈值失活K+电流是由High TEA、(−)维拉帕米和硝苯地平联合阻断的。在这些条件下记录到的电流是异地黄毒素敏感的(Kv4阻滞剂)和α-树突状毒素不敏感的(Kv1.1和Kv1.2阻滞剂)。SP和NKA可使激活低阈值电流的电压依赖性正移10 mV。在对CAPS无反应的神经元中，这种效应是不存在的。NK2受体拮抗剂(MEN10376)可完全逆转SP或NKA对CAPS反应时相神经元K+电流的影响，而PKC抑制剂(双吲哚马来酰亚胺)仅能部分逆转它们的作用。NK1选择性激动剂([Sar9，Met11]-P物质)或用佛波醇12，13-二丁酸酯直接激活PKC，并不改变CAPS反应神经元的放电，但确实抑制在大范围电压下激活的各种类型的K+电流。这些数据表明，激活NK2受体可增加CAPS反应时相传入神经元的兴奋性，这部分是由于抑制和激活异地黄曲霉毒素敏感的Kv4通道的正电压漂移。
Neurokinins (NK) released from terminals of dorsal root ganglion (DRG) neurons may control firing of these neurons by an autofeedback mechanism. In this study we used patch clamp recording techniques to determine if NKs alter excitability of rat L4-S3 DRG neurons by modulating K+ currents. In capsaicin (CAPS)-responsive phasic neurons substance P (SP) lowered action potential (AP) threshold and increased the number of APs elicited by depolarizing current pulses. SP and a selective NK2 agonist, [βAla8]-neurokinin A (4–10) also inhibited low threshold inactivating K+ currents isolated by blocking non-inactivating currents with a combination of high TEA, (−) verapamil and nifedipine. Currents recorded under these conditions were heteropodatoxin-sensitive (Kv4 blocker) and α-dendrotoxin insensitive (Kv1.1 and Kv1.2 blocker). SP and NKA elicited a >10 mV positive shift of the voltage dependence of activation of the low threshold currents. This effect was absent in CAPS-unresponsive neurons. The effect of SP or NKA on K+ currents in CAPS-responsive phasic neurons was fully reversed by an NK2 receptor antagonist (MEN10376) but only partially reversed by a PKC inhibitor (bisindolylmaleimide). An NK1 selective agonist ([Sar9, Met11]-substance P) or direct activation of PKC with phorbol 12,13-dibutyrate, did not change firing in CAPS-responsive neurons, but did inhibit various types of K+ currents that activated over a wide range of voltages. These data suggest that the excitability of CAPS-responsive phasic afferent neurons is increased by activation of NK2 receptors and that this is due in part to inhibition and a positive voltage shift in the activation of heteropodatoxin-sensitive Kv4 channels.
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影响因子：
2.5
作者：
Everill, B;Kocsis, JD
通讯作者：
Kocsis, JD
影响因子：
2.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
2003-10-17
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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