The effects of volatile aromatic anesthetics on voltage-gated Na+ channels expressed in Xenopus oocytes.
The effects of volatile aromatic anesthetics on voltage-gated Na+ channels expressed in Xenopus oocytes.
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挥发性芳族麻醉药对在异爪蟾卵母细胞中表达的电压门控的Na+通道的影响。
DOI：
10.1213/ane.0b013e318184b966
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发表时间：
2008-11
影响因子：
5.7
通讯作者：
Harris RA
中科院分区：
文献类型：
--
作者：
Horishita T;Eger EI 2nd;Harris RA
许多吸入麻醉剂在临床相关浓度下抑制电压门控钠通道，这些药物抑制神经递质释放的结果，至少部分是由于突触前钠通道活性降低。挥发性芳香麻醉药可以抑制n -甲基- d -天冬氨酸（NMDA）受体功能，增强γ-氨基丁酸A （GABAA）受体功能，但这些作用在很大程度上取决于芳香化合物的化学性质。本研究测试了不同芳香麻醉药是否持续抑制钠通道功能。采用全细胞双电极电压钳技术，研究了8种芳香麻醉药对爪蟾卵母细胞中含有β1亚基的Nav1.2钠通道的影响。所有芳香麻醉药在保持电位下抑制INa（钠电流），产生半最大电流（V1/2）（部分去极化）；1,3,5-三氟苯（8±2%）、五氟苯（13±2%）和六氟苯（13±2%）的抑制作用较弱，但苯（37±2%）、氟苯（39±2%）、1,2-二氟苯（48±2%）、1,4-二氟苯（31±3%）和1,2,4-三氟苯（33±1%）的抑制作用较强。其他人也注意到NMDA和GABAA受体的这种二元效应。在保持电位下，INa产生了接近最大电流（-90 mV） （VH-90）的平行抑制作用，但抑制作用要小得多，而六氟苯对该电流的增强作用很小（6±1%）。这些钠通道功能的变化与抑制NMDA受体的有效性、化合物的脂溶性、分子体积和阳离子-π相互作用有关。芳香族化合物对钠通道门控动力学的作用是不同的，这可能是它们不同抑制作用的基础。吸入麻醉剂的MAC浓度产生的抑制范围表明，钠通道抑制可能是这些麻醉剂作用的基础，而不是其他的。
Many inhaled anesthetics inhibit voltage-gated sodium channels at clinically relevant concentrations, and suppression of neurotransmitter release by these agents results, at least partly, from decreased presynaptic sodium channel activity. Volatile aromatic anesthetics can inhibit N-methyl-D-aspartate (NMDA) receptor function and enhance γ-amino butyric acid A (GABAA) receptor function, but these effects depend strongly on the chemical properties of the aromatic ompounds. The present study tested whether diverse aromatic anesthetics consistently inhibit sodium channel function. We studied the effect of eight aromatic anesthetics on Nav1.2 sodium channels with β1 subunits, using whole-cell, two-electrode voltage-clamp techniques in Xenopus oocytes. All aromatic anesthetics inhibited INa (sodium currents) at a holding potential which produce half-maximal current (V1/2) (partial depolarization); inhibition was modest with 1,3,5-trifluorobenzene (8 ± 2%), pentafluorobenzene (13 ± 2%), and hexafluorobenzene (13 ± 2%), but greater with benzene (37 ± 2%), fluorobenzene (39 ± 2%), 1,2-difluorobenzene (48 ± 2%), 1,4-difluorobenzene (31 ± 3%), and 1,2,4-trifluorobenzene (33 ± 1%). Such dichotomous effects were noted by others for NMDA and GABAA receptors. Parallel, but much smaller inhibition, was found for INa at a holding potential which produced near maximal current (−90 mV) (VH-90), and hexafluorobenzene caused small (6 ± 1%) potentiation of this current. These changes in sodium channel function were correlated with effectiveness for inhibiting NMDA receptors, with lipid solubility of the compounds, with molecular volume, and with cation-π interactions. Aromatic compounds vary in their actions on the kinetics of sodium channel gating and this may underlie their variable inhibition. The range of inhibition produced by MAC concentrations of inhaled anesthetics indicates that sodium channel inhibition may underlie the action of some of these anesthetics but not others.
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影响因子：
5.7
作者：
Solt, K;Ii, EIE;Raines, DE
通讯作者：
Raines, DE
DOI：
10.1124/jpet.102.044685
发表时间：
2003-03-01
影响因子：
3.5
作者：
Westphalen, RI;Hemmings, HC
通讯作者：
Hemmings, HC
影响因子：
8.8
作者：
Wu, XS;Sun, JY;Wu, LG
通讯作者：
Wu, LG
影响因子：
8.8
作者：
Wei OuYang;Hemmings, Hugh C., Jr.
通讯作者：
Hemmings, Hugh C., Jr.
DOI：
10.1124/jpet.108.138370
发表时间：
2008-07-01
影响因子：
3.5
作者：
Horishita, Takafumi;Harris, R. Adron
通讯作者：
Harris, R. Adron