GABA(A) receptor antagonism increases NMDA receptor inhibition by isoflurane at a minimum alveolar concentration.
GABA(A) receptor antagonism increases NMDA receptor inhibition by isoflurane at a minimum alveolar concentration.
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DOI：
10.1111/j.1467-2995.2011.00605.x
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发表时间：
2011-05
影响因子：
1.7
通讯作者：
Brosnan RJ
中科院分区：
文献类型：
--
作者：
Brosnan RJ
在最低肺泡浓度(MAC)时，异氟醚增强GABAA受体电流，抑制NMDA受体电流，这些作用可能是产生麻醉的重要因素。然而，异氟醚对GABAA受体的调节作用比NMDA受体更强。这项研究的目的是测试如果异氟醚对GABAA受体的作用降低，它是否会作为更有效的NMDA受体拮抗剂发挥作用。前瞻性实验研究。14只10周龄雄性SD大鼠，体重269±12g，在异氟醚麻醉下留置腰椎蛛网膜下腔导管。2d后，用异氟醚麻醉大鼠，鞘内注入含有GABA受体拮抗剂−-1印防毒素0或1 mg kg的人工脑脊液于1μL分钟−1，然后用标准尾部夹闭技术测定基线异氟醚的最低生活质量。然后静脉注射N-甲基-D-天冬氨酸受体拮抗剂MK80 1(地佐西平)0.5 mg·kg-1·−-1。与对照组相比，印防己毒素使异氟醚MAC增加了16%。MK801显著降低了对照组大鼠异氟醚MAC的0.72%，而接受鞘内印防己毒素的大鼠则减少了0.47%。印防己毒素组中较小的MK801 MAC保留效应与异氟烷对这些动物的NMDA拮抗作用较大是一致的，因为这表明MK801可以作用于降低异氟烷MAC的NMDA受体较少。减少异氟烷GABAA增强增加了异氟烷NMDA在MAC的拮抗作用。因此，在MAC的特定通道或受体上的麻醉效应的大小可能取决于在其他受体上的效应。
At the minimum alveolar concentration (MAC), isoflurane potentiates GABAA receptor currents and inhibits NMDA receptor currents, and these actions may be important for producing anesthesia. However, isoflurane modulates GABAA receptors more potently than NMDA receptors. The objective of this study was to test whether isoflurane would function as a more potent NMDA receptor antagonist if its efficacy at GABAA receptors was decreased. Prospective experimental study. Fourteen 10-week-old male Sprague–Dawley rats weighing 269 ± 12 g. Indwelling lumbar subarachnoid catheters were surgically placed in isoflurane-anesthetized rats. Two days later, the rats were anesthetized with isoflurane, and artificial CSF containing either 0 or 1 mg kg−1 picrotoxin, a GABAA receptor antagonist, was infused intrathecally at 1 μL minute−1. The baseline isoflurane MAC was then determined using a standard tail clamp technique. MK801 (dizocilpine), an NMDA receptor antagonist, was then administered intravenously at 0.5 mg kg−1. Isoflurane MAC was re-measured. Picrotoxin increased isoflurane MAC by 16% compared to controls. MK801 significantly decreased isoflurane MAC by 0.72% of an atmosphere in controls versus 0.47% of an atmosphere in rats receiving intrathecal picrotoxin. A smaller MK801 MAC-sparing effect in the picrotoxin group is consistent with greater NMDA antagonism by isoflurane in these animals, since it suggests that fewer NMDA receptors are available upon which MK801 could act to decrease isoflurane MAC. Decreasing isoflurane GABAA potentiation increases isoflurane NMDA antagonism at MAC. Hence, the magnitude of an anesthetic effect on a given channel or receptor at MAC may depend upon effects at other receptors.
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