Developmental change in GABAA receptor desensitization kinetics and its role in synapse function in rat cortical neurons
Developmental change in GABAA receptor desensitization kinetics and its role in synapse function in rat cortical neurons
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DOI：
10.1111/j.1469-7793.2000.t01-5-00003.xm
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发表时间：
2000-01-01
影响因子：
5.5
通讯作者：
Poulter, MO
中科院分区：
文献类型：
--
作者：
Hutcheon, B;Morley, P;Poulter, MO
1.本研究观察了胚胎大鼠皮层锥体神经元GABA（A）受体突触的成熟。比较GABA（A）、受体介导的微小突触后电流（mPSC）的衰减动力学和GABA在离体膜片中诱发的反应动力学.快速灌注1或10 mM GABA的膜补丁诱发电流与不同的脱敏时间过程中的年轻和老年神经元。对于体外培养4天以上的神经元（DIV），GABA（A）电流具有快速脱敏成分（中位数约为3 ms），这在年轻神经元的斑片中很少见。相比之下，mPSC在2-4 DIV时表现出相当快的衰变成分，随着进一步发育而变得更加突出，尽管其时间常数的中值保持不变。选择性α 3亚基阳性调节剂SB-205384在体外任何时间对mPSC均无影响，但增强突触外活性。这表明突触成熟不是通过早期胚胎GABA（A）受体亚型逐渐交换为成人形式来进行的。在所有年龄段，mPSC的动力学特性是不均匀的。这种异质性扩展到来自单个神经元的mPSC水平，并且可能是突触功能的正常方面。这些结果表明，发育中的神经元中的抑制性突触能够选择性地捕获具有快速脱敏动力学的GABA（A）受体。这种功能偏好可能反映了胚胎GABA（A）受体从内向型营养能力到与信息处理有关的作用的发育转折点。
1. We examined the maturation of GABA(A) receptor synapses in cortical pyramidal neurons cultured from embryonic rats. The decay kinetics of GABA(A), receptor-mediated miniature postsynaptic currents (mPSCs) were compared with those of responses evoked by GABA in excised membrane patches.2. Fast perfusion of 1 or 10 mM GABA on membrane patches evoked currents with different desensitizing time courses in young and old neurons. For neurons older than 4 days in vitro (DIV), GABA(A) currents had a fast component of desensitization (median approximate to 3 ms) seldom seen in patches from younger neurons. In contrast, mPSCs exhibited a substantial fast component of decay at 2-4 DIV that became more prominent with further development although the median value of its time constant remained unchanged.3. The selective alpha 3 subunit positive modulator SB-205384 had no effect on mPSCs at any time in vitro but potentiated extrasynaptic activity. This suggests that synapse maturation does not proceed by a gradual exchange of early embryonic GABA(A) receptor subforms for adult forms.4. At all ages, the kinetic properties of mPSCs were heterogeneous. This heterogeneity extended to the level of mPSCs from single neurons and may be a normal aspect of synaptic functioning.5. These results suggest that inhibitory synapses in developing neurons are capable of selectively capturing GABA(A) receptors having fast desensitization kinetics. This functional preference probably reflects the developmental turning point from an inwardly looking trophic capacity of embryonic GABA(A) receptors to a role concerned with information processing.