Isoflurane inhibits transmitter release and the presynaptic action potential
Isoflurane inhibits transmitter release and the presynaptic action potential
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DOI：
10.1097/00000542-200403000-00029
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发表时间：
2004-03-01
期刊：
影响因子：
8.8
通讯作者：
Wu, LG
中科院分区：
文献类型：
--
作者：
Wu, XS;Sun, JY;Wu, LG
背景：异氟醚抑制许多突触的兴奋性突触后电流(EPSC)。越来越多的证据表明，这与突触前机制有关。然而，突触前的贡献程度还没有得到定量的研究。为了评估突触前的贡献，作者比较了异氟醚对突触前电容跳跃和突触后谷氨酸受体介导的EPSC在大鼠脑干帽状突触的影响。作者确定了异氟醚是否会影响从神经末梢记录的动作电位的波形。结果：0.35~1~05 mm异氟醚使EPSC减少，突触前电容跳跃程度相似，而不影响小型EPSC(量子大小指标)，提示异氟醚主要通过减少谷氨酸的释放抑制EPSC。异氟醚使突触前动作电位降低约3-8%。EPSC与突触前动作电位幅值的10.2次方成正比。根据这种关系，在异氟醚引起的EPSC抑制中，突触前动作电位的抑制贡献了62-78%。结论：异氟醚主要通过抑制递质释放来抑制EPSC。异氟醚降低突触前动作电位幅度，这可能是异氟醚抑制EPSC的重要机制之一。
Background: isoflurane inhibits the excitatory postsynaptic current (EPSC) at many synapses. Accumulated evidence suggests the involvement of a presynaptic mechanism. However, the extent of the presynaptic contribution has not been quantitatively studied. Furthermore, the mechanism underlying the presynaptic contribution remains unclear.Methods: To estimate the presynaptic contribution, the authors compared the effects of isoflurane on the presynaptic capacitance jump, which is proportional to vesicle release, and the postsynaptic glutamate receptor-mediated EPSC at a calyx-type synapse in rat brainstem. The authors determined whether isoflurane affects the waveform of the action potential recorded from nerve terminals. By studying the relation between the EPSC and the presynaptic action potential at the same synapse, the authors determined whether isoflurane inhibits the EPSC by decreasing the presynaptic action potential.Results: lsoflurane at 0.35-1-05 mm reduced the EPSC and the presynaptic capacitance jump to a similar degree without affecting the miniature EPSC (an indicator of quantal size), suggesting that isoflurane inhibits the EPSC predominantly by reducing glutamate release. isoflurane reduced the presynaptic action potential by approximately 3-8%. The EPSC was proportional to the presynaptic action potential amplitude raised to a power of 10.2. Based on this relation, inhibition of the presynaptic action potential contributed to 62-78% of isoflurane-induced inhibition of the EPSC.Conclusions: isoflurane inhibits the EPSC predominantly by inhibition of transmitter release. lsoflurane reduces the presynaptic action potential amplitude, which may contribute significantly to its inhibitory effect on the EPSC.