Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane
Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane
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DOI：
10.1113/jphysiol.2005.086579
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发表时间：
2005-07-01
影响因子：
5.5
通讯作者：
Todorovic, SM
中科院分区：
文献类型：
--
作者：
Joksovic, PM;Bayliss, DA;Todorovic, SM
由丘脑网状核（nRT）中的T型Ca2+通道产生的电流在涉及相互连接的皮层和丘脑神经元的低振幅振荡爆发的产生中起关键作用，并且与觉醒和睡眠状态以及癫痫发作有关。在这里，我们表明，在年轻大鼠的脑切片中，两个动力学不同的T型钙电流存在于nRT神经元，缓慢失活电流只表达在近端树突，快速失活电流主要表达在索马。镍在阻断快电流（IC50 64 μ m）方面的效力是慢电流（IC50 107 μ m）的两倍。卤化挥发性麻醉剂安氟醚阻断这两种电流，但只有缓慢失活电流受到影响，电压依赖性的方式。缓慢的树突状电流是必不可少的低阈值钙峰（ITS）的产生，和安氟醚和镍也抑制LTS和神经元爆发放电的浓度，阻断孤立的T电流。细胞索马和nRT神经元近端树突中表达的T电流的微分动力学特性表明，不同的亚细胞隔室可能表现出不同的膜特性，以响应小的膜去极化。此外，由于在临床麻醉过程中，恩氟烷和其他挥发性麻醉剂在nRT神经元中阻断两种不同的T电流的浓度范围内发生，我们的研究结果表明，这些作用可能有助于麻醉剂的一些重要临床作用。
Currents arising from T-type Ca2+ channels in nucleus reticularis thalami (nRT) play a critical role in generation of low-amplitude oscillatory bursting involving mutually interconnected cortical and thalamic neurones, and are implicated in the state of arousal and sleep, as well as seizures. Here we show in brain slices from young rats that two kinetically different T-type Ca2+ currents exist in nRT neurones, with a slowly inactivating current expressed only on proximal dendrites, and fast inactivating current predominantly expressed on soma. Nickel was about twofold more potent in blocking fast (IC50 64 mu m) than slow current (IC50 107 mu m). The halogenated volatile anaesthetic enflurane blocked both currents, but only the slowly inactivating current was affected in voltage-dependent fashion. Slow dendritic current was essential for generation of low-threshold Ca2+ spikes (ITS), and both enflurane and nickel also suppressed LTS and neuronal burst firing at concentrations that blocked isolated T currents. Differential kinetic properties of T currents expressed in cell soma and proximal dendrites of nRT neurones indicate that various subcellular compartments may exhibit different membrane properties in response to small membrane depolarizations. Furthermore, since blockade of two different T currents in nRT neurones by enflurane and other volatile anaesthetics occurs within concentrations that are relevant during clinical anaesthesia, our findings suggest that these actions could contribute to some important clinical effects of anaesthetics.