Mechanism of anesthesia revealed by shunting actions of isoflurane on thalamocortical neurons
Mechanism of anesthesia revealed by shunting actions of isoflurane on thalamocortical neurons
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DOI：
10.1152/jn.1999.81.4.1795
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发表时间：
1999-04-01
影响因子：
2.5
通讯作者：
Puil, E
中科院分区：
文献类型：
--
作者：
Ries, CR;Puil, E
用幼年大鼠丘脑脑片和全细胞记录技术，观察了异氟醚(IFL)水处理对腹基底区中继神经元强直放电和爆发放电活动的影响。在与体内麻醉相同的浓度下，IFL以可逆的和浓度依赖的方式诱导超极化和膜电导增加(离子机制详见配套文件)。电导的增加使去极化脉冲的有效性短路，是抑制动作电位紧张性放电的主要原因。尽管IFL诱导的超极化在理论上应该促进爆发，但分流阻断了低阈值钙峰(LTS)和相关的动作电位爆发放电以及高阈值钙峰(HTS)。增加去极化测试脉冲或超极化预脉冲的幅度或增加超极化预脉冲的持续时间，部分逆转了对LTS脉冲的封锁。在产生LTS的T型钙电流的电压钳实验中，IFL降低了外加电压的空间分布，从而削弱了空间距离T通道的激活。尽管IFL可能增加了树突漏电导或减少了树突状钙电流，但体细胞分流似乎阻止了LTS和HTS的启动以及它们向轴突的电渗性繁殖。综上所述，IFL使丘脑皮质神经元超极化，并使电压依赖性钠电流和钙电流分流。考虑到丘脑在传递不同感觉方式(即躯体感觉、听觉和视觉)和运动信息中的重要性，以及皮质丘脑皮质环在调节意识方面的重要性，丘脑皮质神经元的分流放电活动将有助于体内麻醉的产生。
By using thalamic brain slices from juvenile rats and the whole cell recording technique, we determined the effects of aqueous applications of the anesthetic isoflurane (IFL) on tonic and burst firing activities of ventrobasal relay neurons. At concentrations equivalent to those used for in vivo anesthesia, IFL induced a hyperpolarization and increased membrane conductance in a reversible and concentration-dependent manner (ionic mechanism detailed in companion paper). The increased conductance short-circuited the effectiveness of depolarizing pulses and was the main cause for inhibition of tonic firing of action potentials. Despite the IFL-induced hyperpolarization, which theoretically should have promoted bursting, the shunt blocked the low-threshold Ca2+ spike (LTS) and associated burst firing of action potentials as well as the high-threshold Ca2+ spike (HTS). Increasing the amplitude of either the depolarizing test pulse or hyperpolarizing prepulse or increasing the duration of the hyperpolarizing prepulse partially reversed the blockade of the LTS burst. In voltage-clamp experiments on the T-type Ca2+ current, which produces the LTS, IFL decreased the spatial distribution of imposed voltages and hence impaired the activation of spatially distant T channels. Although IFL may have increased a dendritic leak conductance or decreased dendritic Ca2+ currents, the somatic shunt appeared to block initiation of the LTS and HTS as well as their electrotonic propogation to the axon hillock. In summary, IFL hyperpolarized thalamocortical neurons and shunted voltage-dependent Na+ and Ca2+ currents. Considering the importance of the thalamus in relaying different sensory modalities (i.e., somatosensation, audition, and vision) and motor information as well as the corticothalamocortical loops in mediating consciousness, the shunted firing activities of thalamocortical neurons would be instrumental for the production of anesthesia in vivo.