Persistent ictal-like activity in rat entorhinal/perirhinal cortex following washout of 4-aminopyridine.
Persistent ictal-like activity in rat entorhinal/perirhinal cortex following washout of 4-aminopyridine.
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DOI：
10.1016/j.eplepsyres.2011.01.017
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发表时间：
2011-05
影响因子：
2.2
通讯作者：
Perkins, Katherine L.
中科院分区：
文献类型：
--
作者：
Salah, Alejandro;Perkins, Katherine L.
将4-氨基吡啶（4-AP，100 μM）溶于含0.6 mM Mg 2+和1.2 mM Ca 2+的溶液中，应用于成年大鼠脑的前额叶-内嗅-嗅周切片，可诱导内嗅和嗅周皮质的癫痫样活动，如电生理场电位记录所示。洗脱4-AP后，发作样活动持续存在。这种持续性表明切片发生了变化，因此在没有惊厥剂4-AP的情况下，它现在是“癫痫性的”。诱导持续发作样活性依赖于二价阳离子的浓度在4-AP曝光，也就是说，虽然4-AP引起发作样活性在约一半的切片在含有1.6 mM Mg 2+和2.0 mM Ca 2+的溶液中，这种发作样活性没有持续洗脱后的4-AP。持续发作样癫痫样活动的表达需要离子型谷氨酸介导的突触传递：在4-AP洗脱后应用AMPA/红藻氨酸受体拮抗剂NBQX可降低持续性癫痫样活动，而NBQX和NMDA受体拮抗剂D-AP 5的联合应用可完全阻断该活动。为了研究诱导持续性癫痫样活动的机制，在引入4-AP之前应用了几种试剂。应用D-AP 5并不阻断4-AP引入后发作样活性的发作，但确实阻止了4-AP洗脱后发作样活性的持续。与此相反，诱导的持续性癫痫样活动并没有阻止同时应用组I代谢型谷氨酸受体（mGluR）拮抗剂LY 367385和MPEP或通过应用蛋白质合成抑制剂放线菌酮。总之，我们已经表征了一种新的体外癫痫模型，其中癫痫样活性的诱导依赖于NMDA受体活化，但不依赖于I组mGluR活化或蛋白质合成。
Application of 4-aminopyridine (4-AP, 100 μM) in a solution containing 0.6 mM Mg2+ and 1.2 mM Ca2+ to hippocampal-entorhinal-perirhinal slices of adult rat brain induced ictal-like epileptiform activity in entorhinal and perirhinal cortices as revealed by electrophysiological field potential recordings. The ictal-like activity persisted after washing out the 4-AP. This persistence indicated that a change had occurred in the slice so that it was now “epileptic” in the absence of the convulsant 4-AP. Induction of persistent ictal-like activity was dependent upon the concentration of divalent cations during 4-AP exposure; that is, although 4-AP caused ictal-like activity in approximately half the slices in solution containing 1.6 mM Mg2+ and 2.0 mM Ca2+, this ictal-like activity did not persist upon washout of the 4-AP. Expression of the persistent ictal-like epileptiform activity required ionotropic glutamate-mediated synaptic transmission: application of the AMPA/kainate receptor antagonist NBQX after 4-AP washout reduced persistent ictal-like activity, and the combined application of NBQX and the NMDA receptor antagonist D-AP5 completely blocked it. In order to investigate the mechanism of induction of persistent ictal-like activity, several agents were applied before the introduction of 4-AP. Application of D-AP5 did not block the onset of ictal-like activity upon introduction of 4-AP but did prevent the persistence of the ictal-like activity upon washout of the 4-AP. In contrast, induction of persistent ictal-like activity was not prevented by simultaneous application of the group I metabotropic glutamate receptor (mGluR) antagonists LY 367385 and MPEP or by application of the protein synthesis inhibitor cycloheximide. In conclusion, we have characterized a new in vitro model of epileptogenesis in which induction of ictal-like activity is dependent upon NMDA receptor activation but not upon group I mGluR activation or protein synthesis.
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