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小鼠丘脑网状核中功能性超极化激活电流(Ih)的表达。

Expression of a functional hyperpolarization-activated current (Ih) in the mouse nucleus reticularis thalami.

作者信息

Rateau Y, Ropert N

机构信息

Laboratoire de Neurophysiologie et Nouvelles Microscopies, Institut National de la Santé et de la Recherche Médicale U603, Université Paris Descartes, Paris, France.

出版信息

J Neurophysiol. 2006 May;95(5):3073-85. doi: 10.1152/jn.00922.2005.

DOI:10.1152/jn.00922.2005
PMID:16617177
Abstract

The GABAergic neurons of the nucleus reticularis thalami (nRT) express the type 2 hyperpolarization-activated cAMP-sensitive (HCN2) subunit mRNA, but surprisingly, they were reported to lack the hyperpolarization-activated (Ih) current carried by this subunit. Using the voltage-clamp recordings in the thalamocortical slice preparation of the newborn and juvenile mice (P6-P23), we demonstrate that, in the presence of 1 mM barium (Ba2+), the nRT neurons express a slow hyperpolarization-activated inward current, suggesting that the Ih is present but masked in control conditions by K+ leak currents. We investigate the identity of the hyperpolarization-activated current in the nRT by studying its physiological and pharmacological profile in presence of Ba2+. We show that it has voltage- and time-dependent properties typical of the Ih, that it is blocked by cesium and ZD7288, two blockers of the Ih, and that it is carried both by the K+ and Na+ ions. We could also alter the gating characteristics of the hyperpolarization-activated current in the nRT by adding a nonhydrolysable analogue of cAMP to the pipette solution. Finally, using the current-clamp recording, we showed that blocking the hyperpolarization-activated current induced an hyperpolarization correlated with an increase of the R(in) of the nRT neurons. In conclusion, our results demonstrate that the nRT neurons express the Ih with slow kinetics similar to those described for the homomeric HCN2 channels, and we show that the Ih of the nRT contributes to the excitability of the nRT neurons in normal conditions.

摘要

丘脑网状核(nRT)的γ-氨基丁酸能神经元表达2型超极化激活的环磷酸腺苷敏感(HCN2)亚基mRNA,但令人惊讶的是,据报道它们缺乏由该亚基携带的超极化激活(Ih)电流。利用新生和幼年小鼠(P6 - P23)丘脑皮质脑片制备中的电压钳记录,我们证明,在存在1 mM钡(Ba2 +)的情况下,nRT神经元表达一种缓慢的超极化激活内向电流,这表明Ih存在,但在对照条件下被K +泄漏电流掩盖。我们通过研究其在Ba2 +存在下的生理和药理学特征来探究nRT中这种超极化激活电流的特性。我们表明它具有Ih典型的电压和时间依赖性特性,它被Ih的两种阻滞剂铯和ZD7288阻断,并且它由K +和Na +离子携带。我们还可以通过向移液管溶液中添加一种不可水解的环磷酸腺苷类似物来改变nRT中超极化激活电流的门控特性。最后,使用电流钳记录,我们表明阻断超极化激活电流会诱导一种超极化,这与nRT神经元的输入电阻(Rin)增加相关。总之,我们的结果表明nRT神经元表达具有与同源HCN2通道所描述的相似的缓慢动力学的Ih,并且我们表明nRT的Ih在正常条件下有助于nRT神经元的兴奋性。

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