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首页> 外文期刊>The European Journal of Neuroscience >Presynaptic source of quantal size variability at GABAergic synapses in rat hippocampal neurons in culture.
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Presynaptic source of quantal size variability at GABAergic synapses in rat hippocampal neurons in culture.

机译：在培养的大鼠海马神经元中，GABA能突触的突触前数量大小变异性来源。

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Abstract The variability of quantal size depends on both presynaptic (profile of the neurotransmitter concentration in the cleft) and postsynaptic (number and gating properties of postsynaptic receptors) factors. Here we have examined the possibility that at nonsaturated synapses in cultured hippocampal neurons, changes in both the transmitter concentration peak and its clearance from the synaptic cleft may influence the variability of spontaneous miniature synaptic GABAergic currents (mIPSCs). We found that, in contrast to the slow-off GABA(A) receptor antagonist bicuculline, fast-off competitive antagonists such as SR-95103 and TPMPA differentially blocked small and large mIPSCs. In the presence of flurazepam, a drug believed to increase the affinity of GABA for GABA(A)R, small mIPSCs were enhanced more efficiently than large events. Moreover, the addition of dextran, which increases the viscosity of the extracellular fluid, preferentially increased small mIPSCs with respect to large ones. These observations suggest that changes in the concentration peak and the speed of GABA clearance in the cleft may be an important source of synaptic variability. The study of the correlation between peak amplitude and kinetics of mIPSCs allowed determination of the relative contribution of transmitter peak concentration vs. time of GABA clearance. Small synaptic responses were associated with fast onset and decay kinetics while large amplitude currents were asociated with slow kinetics, indicating a crucial role for GABA synaptic clearance in variability of mIPSCs. By using model simulations we were able to estimate the range of variability of both the concentration and the speed of clearance of the GABA transient in the synaptic cleft.
机译：摘要量子大小的可变性取决于突触前（裂隙中神经递质的浓度分布）和突触后（突触后受体的数量和门控特性）因素。在这里，我们研究了在培养的海马神经元的非饱和突触中，递质浓度峰值及其从突触间隙清除的变化可能影响自发微型突触GABA能电流（mIPSC）的可能性。我们发现，与缓慢释放的GABA（A）受体拮抗剂双瓜氨酸相比，快速释放的竞争性拮抗剂（例如SR-95103和TPMPA）差异性地阻断了大小型mIPSC。在氟拉西m的存在下，一种被认为可以增加GABA对GABA（A）R的亲和力的药物，与大事件相比，小mIPSC的增强效率更高。此外，右旋糖酐的添加增加了细胞外液的粘度，相对于大的mIPSC，优先增加了小的mIPSC。这些观察结果表明，裂隙中浓度峰值的变化和GABA清除的速度可能是突触变异的重要来源。对mIPSCs峰幅度和动力学之间相关性的研究可以确定发射峰浓度与GABA清除时间的相对贡献。小的突触反应与快速发作和衰变动力学相关，而大振幅电流与缓慢的动力学相关，表明GABA突触清除在mIPSC变异性中起关键作用。通过使用模型仿真，我们能够估计突触间隙中GABA瞬变的浓度和清除速度的变化范围。

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