Increased NMDA receptor inhibition at an increased Sevoflurane MAC.
Increased NMDA receptor inhibition at an increased Sevoflurane MAC.
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DOI：
10.1186/1471-2253-12-9
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发表时间：
2012-06-06
影响因子：
2.2
通讯作者：
Thiesen R
中科院分区：
文献类型：
--
作者：
Brosnan RJ;Thiesen R
七氟醚可以增强甘氨酸受体电流，并适度降低NMDA受体电流，这两种电流都可能导致不动。七氟醚在最低肺泡浓度（MAC）下对NMDA受体的适度拮抗作用可能与其他抑制离子通道的大增强相互关联。如果是这样，那么甘氨酸受体效价的降低应该会增加七氟醚在MAC时对NMDA受体的拮抗作用。我们在14只麻醉大鼠中手术置入腰椎蛛网膜下腔导管。第二天用七氟醚麻醉大鼠，用尾钳法测量输注前七氟醚MAC，一式两份。将含有0或4 mg/mL士的宁的人工脑脊液（aCSF）以4 μL/min的速度注入鞘内，测定输注后基线七氟烷MAC。最后，以4 μL/min的速度给药含有士的宁（0或4 mg/mL） + 0.4 mg/mL二唑西平（MK-801）的aCSF，测定二唑西平七氟化后的MAC。预注七氟醚的MAC为2.26%。单独鞘内aCSF不影响MAC，但鞘内士的宁显著增加了七氟醚的需求量。添加二唑西平显著降低了所有大鼠的MAC，但未鞘内注入士的宁的大鼠的MAC下降幅度是鞘内注入士的宁的大鼠的两倍，差异有统计学意义（P < 0.005），这与七氟醚在接受士的宁的大鼠中增加NMDA受体拮抗作用一致。甘氨酸受体拮抗剂可增加七氟醚在MAC处对NMDA受体的拮抗剂作用。因此，麻醉对给定离子通道的影响程度可能取决于其对调节神经元兴奋性的其他受体的影响程度。
Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC) could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF) containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL) plus 0.4 mg/mL dizocilpine (MK-801) was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P < 0.005) difference that is consistent with increased NMDA receptor antagonism by sevoflurane in rats receiving strychnine. Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.
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