High Intracellular Chloride Slows the Decay of Glycinergic Currents
High Intracellular Chloride Slows the Decay of Glycinergic Currents
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DOI：
10.1523/jneurosci.3890-08.2008
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发表时间：
2008-11-05
影响因子：
5.3
通讯作者：
Beato, Marco
中科院分区：
文献类型：
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作者：
Pitt, Samantha J.;Sivilotti, Lucia G.;Beato, Marco
本机和重组甘氨酸受体介导的电流的时间过程进行了检查与快速激动剂的应用程序，外向补丁和单通道记录的组合。由甘氨酸的短暂饱和脉冲诱发的电流的失活时间常数受到细胞膜的胞内侧上的氯离子浓度的深刻影响。当细胞内氯化物从低水平（10 mM）（与在活的成熟神经元中观察到的相似）增加到131 mM（“对称”氯化物，常用于移液管内部溶液）时，失活慢三倍。单通道分析表明，高氯离子对通道关闭速率的影响最大，与我们在细胞附着模式（其中通道处于生理细胞内氯离子浓度）中估计的值相比，将其减慢了2倍。当记录幼年大鼠离体脊髓运动神经元甘氨酸能诱发的突触电流时，我们的结果表明，完整神经元甘氨酸能突触抑制的时间过程比测量估计的要快得多在对称氯化物中，并且可以通过在生理或病理条件下可能发生的范围内的细胞内氯化物浓度的变化来调节。
The time course of currents mediated by native and recombinant glycine receptors was examined with a combination of rapid agonist applications to outside-out patches and single-channel recording. The deactivation time constant of currents evoked by brief, saturating pulses of glycine is profoundly affected by the chloride concentration on the intracellular side of the cell membrane. Deactivation was threefold slower when intracellular chloride was increased from a low level (10 mM), similar to that observed in living mature neurons, to 131 mM ("symmetrical" chloride, often used in pipette internal solutions). Single-channel analysis revealed that high chloride has its greatest effect on the channel closing rate, slowing it by a factor of 2 compared with the value we estimated in the cell-attached mode (in which the channels are at physiological intracellular chloride concentrations). The same effect of chloride was observed when glycinergic evoked synaptic currents were recorded from juvenile rat spinal motoneurons in vitro, because the decay time constant was reduced from similar to 7 ms to similar to 3 ms when cells were dialyzed with 10 mM chloride intracellular recording solution.Our results indicate that the time course of glycinergic synaptic inhibition in intact neurons is much faster than is estimated by measurements in symmetrical chloride and can be modulated by changes in intracellular chloride concentration in the range that can occur in physiological or pathological conditions.