Developmental changes of GABA synaptic transient in cerebellar granule cells
Developmental changes of GABA synaptic transient in cerebellar granule cells
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DOI：
10.1124/mol.104.006437
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发表时间：
2005-04-01
影响因子：
3.6
通讯作者：
Mozrzymas, JW
中科院分区：
文献类型：
--
作者：
Barberis, A;Lu, CY;Mozrzymas, JW
突触电流的时间过程很大程度上取决于突触后受体的微观门控和突触神经递质浓度的时间分布。尽管多项证据表明 GABA 能突触电流时间进程的发育变化与突触后受体的转换明显相关，但对发育过程中 GABA 释放的改变知之甚少。为了解决这个问题，我们研究了体外培养 6 至 8 天 (DIV)（“年轻”）和 12 至 14 DIV（“老年”）的神经元中微型抑制性突触后电流 (mIPSC) 对快速解离竞争性拮抗剂 1,2,5,6-四氢吡啶4-基)甲基次膦酸 (TPMPA) 的敏感性。年轻神经元中记录的 mIPSC 对 TPMPA 的阻断显着具有更强的抵抗力。这一观察结果被解释为年轻神经元中更强的 GABA 释放导致 TPMPA 从 GABA A 受体更有效地置换的结果。发育过程中 mIPSC 对 TPMPA 敏感性的变化不受 α(1) 亚基删除的影响，这支持了其突触前起源。第二种快速解离拮抗剂 SR-95103 [ 2-( 羧基- 3'- 丙基)- 3- 氨基- 4- 甲基- 6- 苯基哒嗪氯化物 ] 对年轻、年老和 α(1) -/- 神经元的影响与 TPMPA 获得的效果在性质上相同。此外，对当前对超快 GABA 应用的反应的分析表明，DIV 6 至 8 和 DIV 12 至 14 神经元中 TPMPA 的解离率没有显着差异，排除了 TPMPA 差异作用的突触后机制。因此，我们提供的证据表明突触前 GABA 单量释放受到发育调节。
The time course of synaptic currents is largely determined by the microscopic gating of the postsynaptic receptors and the temporal profile of the synaptic neurotransmitter concentration. Although several lines of evidence indicate that developmental changes of GABAergic synaptic current time course are clearly correlated with a switch in postsynaptic receptors, much less is known about the modification of GABA release during development. To address this issue, we studied the sensitivity of miniature inhibitory postsynaptic currents ( mIPSCs) to a quickly dissociating competitive antagonist, 1,2,5,6- tetrahydropyridine4- yl) methylphosphinic acid ( TPMPA), in neurons cultured for 6 to 8 days in vitro ( DIV) (" young") and for 12 to 14 DIV (" old"). mIPSCs recorded in young neurons were significantly more resistant to the block by TPMPA. This observation was interpreted as a consequence of a more efficient displacement of TPMPA from GABA A receptors caused by a stronger GABA release in young neurons. The change in mIPSC sensitivity to TPMPA during development was not affected by the deletion of alpha(1) subunit, supporting its presynaptic origin. The effects of a second quickly dissociating antagonist, SR- 95103 [ 2-( carboxy- 3'- propyl)- 3- amino- 4- methyl- 6- phenylpyridazinium chloride], on young, old, and alpha(1) -/- neurons were qualitatively the same as those obtained with TPMPA. Moreover, the analysis of current responses to ultrafast GABA applications showed that the unbinding rates of TPMPA in DIV 6 to 8 and in DIV 12 to 14 neurons are not significantly different, ruling out the postsynaptic mechanism of differential TPMPA action. Thus, we provide evidence that presynaptic GABA uniquantal release is developmentally regulated.