Thalamic Kv7 channels: pharmacological properties and activity control during noxious signal processing
Thalamic Kv7 channels: pharmacological properties and activity control during noxious signal processing
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DOI：
10.1111/bph.13113
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发表时间：
2015-06-01
影响因子：
7.3
通讯作者：
Budde, Thomas
中科院分区：
文献类型：
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作者：
Cerina, Manuela;Szkudlarek, Hanna J.;Budde, Thomas
背景与目的丘脑皮层（TC）中继神经元是否存在功能性K（v）7通道以及K+通道中M电流（I-M）对丘脑信号处理的影响一直存在争议。免疫细胞化学证据表明它们存在于这个大脑区域。因此，我们的目的是验证它们的存在，药理学性质和功能的调节神经元的腹侧基底丘脑（VB）。实验方法K（v）7通道的特性进行了结合在体外，在体内和计算机技术与药理学方法。在电生理记录过程中，在急性脑切片中分别应用Retigabine（30 M）和XE 991（20 M），Retigabine和XE 991分别是一种特异性K（v）7通道增强剂和阻断剂。在自由活动的动物在热板tests.Key ResultsK（v）7.2和K（v）7.3亚基记录的行为和神经元activity.Key的影响，研究了丘脑内注射瑞替加滨（3 mM，300 nL）和/或XE 991（2 mM，300 nL）被发现大量表达在TC神经元的小鼠VB。瑞替加滨可激活具有I-M特性的慢K+电流，而XE 991则可抑制该电流。在体外和计算模型中，K（v）7通道激活诱发膜超极化，强直性动作电位放电减少，爆发性放电增加。单单位记录和药物干预表明，在体内I-M激活后，特定的爆发放电增加。A K（v）7通道介导的痛阈增加与较少的VB单位对伤害性刺激的反应有关，并增加了反应神经元的爆发放电。结论和意义K（v）7通道增强改变了躯体感觉活动，可能反映了急性疼痛处理过程中的抗伤害性机制。
Background and PurposeThe existence of functional K(v)7 channels in thalamocortical (TC) relay neurons and the effects of the K+-current termed M-current (I-M) on thalamic signal processing have long been debated. Immunocytochemical evidence suggests their presence in this brain region. Therefore, we aimed to verify their existence, pharmacological properties and function in regulating activity in neurons of the ventrobasal thalamus (VB).Experimental ApproachCharacterization of K(v)7 channels was performed by combining in vitro, in vivo and in silico techniques with a pharmacological approach. Retigabine (30M) and XE991 (20M), a specific K(v)7 channel enhancer and blocker, respectively, were applied in acute brain slices during electrophysiological recordings. The effects of intrathalamic injection of retigabine (3mM, 300nL) and/or XE991 (2mM, 300nL) were investigated in freely moving animals during hot-plate tests by recording behaviour and neuronal activity.Key ResultsK(v)7.2 and K(v)7.3 subunits were found to be abundantly expressed in TC neurons of mouse VB. A slow K+-current with properties of I-M was activated by retigabine and inhibited by XE991. K(v)7 channel activation evoked membrane hyperpolarization, a reduction in tonic action potential firing, and increased burst firing in vitro and in computational models. Single-unit recordings and pharmacological intervention demonstrated a specific burst-firing increase upon I-M activation in vivo. A K(v)7 channel-mediated increase in pain threshold was associated with fewer VB units responding to noxious stimuli, and increased burst firing in responsive neurons.Conclusions and ImplicationsK(v)7 channel enhancement alters somatosensory activity and may reflect an anti-nociceptive mechanism during acute pain processing.