Ries C R, Puil E
Department of Pharmacology and Therapeutics and Department of Anaesthesia, Faculty of Medicine, The University of British Columbia Vancouver, British Columbia V6T 1Z3, Canada.
J Neurophysiol. 1999 Apr;81(4):1795-801. doi: 10.1152/jn.1999.81.4.1795.
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.
通过使用幼年大鼠的丘脑脑片和全细胞记录技术，我们确定了麻醉药异氟烷（IFL）的水溶液对腹侧基底中继神经元的紧张性放电和爆发性放电活动的影响。在与体内麻醉所用浓度相当的浓度下，IFL以可逆且浓度依赖性的方式诱导超极化并增加膜电导（相关离子机制在配套论文中详细阐述）。增加的电导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诱导了超极化，理论上这应该会促进爆发，但分流阻断了低阈值Ca2+尖峰（LTS）以及相关的动作电位爆发性放电以及高阈值Ca2+尖峰（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，可部分逆转对LTS爆发的阻断。在对产生LTS的T型Ca2+电流进行的电压钳实验中，IFL降低了施加电压的空间分布，从而损害了空间上较远的T通道的激活。尽管IFL可能增加了树突漏电导或降低了树突Ca2+电流，但体细胞分流似乎阻断了LTS和HTS的起始以及它们向轴丘的电紧张性传播。总之，IFL使丘脑皮质神经元超极化，并分流电压依赖性Na+和Ca2+电流。考虑到丘脑在传递不同感觉模态（即躯体感觉、听觉和视觉）以及运动信息方面的重要性，以及皮质丘脑皮质环路在介导意识方面的作用，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。
