Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys.
Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys.
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DOI：
10.1186/1471-2202-7-5
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发表时间：
2006-01-12
期刊：
影响因子：
2.4
通讯作者：
MacIver MB
中科院分区：
文献类型：
--
作者：
Winegar BD;MacIver MB
麻醉诱导的CNS抑制被认为涉及神经末梢谷氨酸释放的减少。最近的研究表明，异氟烷通过阻断Na通道减少谷氨酸的释放。为了进一步研究这个问题，我们研究了异氟烷，TTX，细胞外Ca 2+，CNQX和刺激电压（stim）对海马兴奋性突触谷氨酸介导的传递的作用。在大鼠海马脑片上记录到海马CA 1区神经元对Schaffer侧支纤维刺激的EPSPs。异氟烷（350 μM; 1 MAC）可逆性降低EPSP振幅约60%，而易化增加约20%。与以前的研究一致，这些结果表明，突触前的行动，涉及减少兴奋释放耦合网站。通过TTX（60 nM）或降低刺激，EPSP被抑制至可比较的水平，但易化没有改变，表明轴突传导的简单失败。类似地，CNQX（10 μM）部分拮抗突触后谷氨酸受体可降低EPSP振幅，但易化性无变化。然而，EPSP抑郁症低外部Ca 2+（0.8 mM）伴随着增加易化与异氟烷。异氟醚抑郁症的EPSP振幅也可以部分逆转高外部Ca 2+（4 mM），也减少了易化。异氟醚或低钙显著降低了纤维凌空（FV）-EPSP输入-输出曲线的斜率，与对FV的影响很小或没有影响一致。TTX对FV-EPSP曲线斜率无明显影响，提示FV降低是导致EPSP降低的原因。FV对异氟烷具有显著的耐药性。体细胞锋电位电流也不受350 μM（1 MAC）异氟烷的影响。异氟烷抑制FV的EC 50约为2.8 mM（12 vol. %; 8 MAC）。异氟烷似乎可以抑制钠通道下游突触前位点的CA 1突触，这一点可以通过伴随EPSP抑制的易化作用增强来证明。纤维凌空并没有表现出抑郁症的异氟烷，已报告的其他脑区。
Anesthetic-induced CNS depression is thought to involve reduction of glutamate release from nerve terminals. Recent studies suggest that isoflurane reduces glutamate release by block of Na channels. To further investigate this question we examined the actions of isoflurane, TTX, extracellular Ca2+, CNQX and stimulus voltage (stim) on glutamate-mediated transmission at hippocampal excitatory synapses. EPSPs were recorded from CA1 neurons in rat hippocampal brain slices in response to Schaffer-collateral fiber stimulation. Isoflurane (350 μM; 1 MAC) reversibly depressed EPSP amplitudes by ~60% while facilitation increased ~20%. Consistent with previous studies, these results indicate a presynaptic site of action that involves reduced excitation-release coupling. EPSPs were depressed to comparable levels by TTX (60 nM) or lowered stim, but facilitation was not changed, indicating a simple failure of axonal conduction. Similarly, partial antagonism of postsynaptic glutamate receptors with CNQX (10 μM) depressed EPSP amplitudes with no change in facilitation. However, EPSP depression by low external Ca2+ (0.8 mM) was accompanied by an increase in facilitation comparable to isoflurane. Isoflurane depression of EPSP amplitudes could also be partly reversed by high external Ca2+ (4 mM) that also decreased facilitation. Isoflurane or low Ca2+ markedly reduced the slopes of fiber volley (FV)-EPSP input-output curves, consistent with little or no effect on FVs. By contrast, TTX didn't alter the FV-EPSP curve slope, indicating that EPSP depression resulted from FV depression. FVs were remarkably resistant to isoflurane. Somatic spike currents were unaffected by 350 μM (1 MAC) isoflurane as well. The EC50 for isoflurane depression of FVs was ~2.8 mM (12 vol. %; 8 MAC). Isoflurane appears to depress CA1 synapses at presynaptic sites downstream from Na channels, as evident by the increased facilitation that accompanies EPSP depression. Fiber volleys did not exhibit depression by isoflurane, as has been reported for other brain regions.
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影响因子：
9.8
作者：
KENNEDY, RD;GALINDO, AD
通讯作者：
GALINDO, AD
影响因子：
7.3
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