The glutamate transporter EAAT5 works as a presynaptic receptor in mouse rod bipolar cells
The glutamate transporter EAAT5 works as a presynaptic receptor in mouse rod bipolar cells
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谷氨酸转运蛋白 EAAT5 作为小鼠视杆双极细胞的突触前受体
DOI：
10.1113/jphysiol.2006.118281
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
M. Roux
中科院分区：
文献类型：
--
作者：
É. Wersinger;Y. Schwab;J. Sahel;A. Rendon;D. Pow;S. Picaud;M. Roux
膜神经递质转运蛋白通过摄取与Na+和其他离子运动的热力学耦合来控制突触间隙中其底物的浓度。此外，兴奋性氨基酸转运蛋白（EAAT）具有Cl−电导，其由Na+和谷氨酸的联合结合门控，但与谷氨酸的通量不偶联。这种电导在视网膜特异性EAAT 5同种型中特别大。在小鼠视网膜中，我们将EAAT 5定位于视锥和视杆细胞的感光末梢以及视杆双极细胞的轴突末梢。在这些后一种细胞中，在轴突终末上施加谷氨酸引起了在EC 1处逆转的电流，对荷包牡丹碱、TPMPA、士的宁、dl-AP 5、CNQX和MCPG不敏感，但被谷氨酸转运蛋白抑制剂dl-tBOA阻断。此外，双极细胞的短去极化诱发了dl-tBOA和Cd 2+敏感电流，其幅度与谷氨酸诱发电流相当。其动力学表明EAAT 5位于谷氨酸释放位点附近。对于引起最大反应的2 ms去极化，EAAT 5介导的电流携带的电荷是从无长突细胞自发接收的平均抑制性GABA或甘氨酸突触后电流的2至8倍，细胞内EGTA分别为10 mm或0.5 mm。在相互抑制的条件下，可以监测，EAAT 5电流所携带的电荷是1.5倍以上的抑制性突触后电流从无长突细胞。这些结果表明，EAAT 5作为一个主要的抑制性突触前受体在哺乳动物杆双极细胞轴突终末。这种反馈机制可以控制非尖峰神经元的带状突触处的谷氨酸释放，并增加视杆光感受器通路中的时间对比度。
Membrane neurotransmitter transporters control the concentration of their substrate in the synaptic clefts, through the thermodynamic coupling of uptake to the movement of Na+ and other ions. In addition, excitatory amino acid transporters (EAAT) have a Cl− conductance which is gated by the joint binding of Na+ and glutamate, but thermodynamically uncoupled to the flux of glutamate. This conductance is particularly large in the retina‐specific EAAT5 isoform. In the mouse retina, we located EAAT5 in both cone and rod photoreceptor terminals and in axon terminals of rod bipolar cells. In these later cells, application of glutamate on the axon terminal evoked a current that reversed at ECl, was insensitive to bicuculline, TPMPA, strychnine, dl‐AP5, CNQX and MCPG, but blocked by the glutamate transporter inhibitor dl‐tBOA. Furthermore, short depolarizations of the bipolar cells evoked a dl‐tBOA and Cd2+‐sensitive current whose amplitude was comparable to the glutamate‐evoked current. Its kinetics indicated that EAAT5 was located close to the glutamate release site. For 2 ms depolarizations evoking maximal responses, the EAAT5‐mediated current carried between 2 and 8 times more charge as an average inhibitory GABA or glycine postsynaptic current received spontaneously from amacrine cells, with 10 mm or 0.5 mm intracellular EGTA, respectively. In conditions for which reciprocal inhibition could be monitored, the charge carried by the EAAT5 current was 1.5 times larger than the one carried by the inhibitory postsynaptic currents received from amacrine cells. These results indicate that EAAT5 acts as a major inhibitory presynaptic receptor at mammalian rod bipolar cell axon terminals. This feedback mechanism could control glutamate release at the ribbon synapses of a non‐spiking neuron and increase the temporal contrast in the rod photoreceptor pathway.
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影响因子：
2.5
作者：
Kwoon Y. Wong;E. Cohen;J. Dowling
通讯作者：
Kwoon Y. Wong;E. Cohen;J. Dowling
影响因子：
56.9
作者：
SLAUGHTER, MM;MILLER, RF
通讯作者：
MILLER, RF
影响因子：
2.5
作者：
W. Thoreson;E. J. Bryson;K. Rábl
通讯作者：
W. Thoreson;E. J. Bryson;K. Rábl
蝾螈杆中钙电流电压依赖性和振幅的阴离子调制。
DOI：
10.1016/s0005-2736(99)00257-6
发表时间：
2000
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Thoreson,WB;Stella,SL
通讯作者：
Stella,SL