Fast neurotransmitter release triggered by Ca influx through AMPA-type glutamate receptors
Fast neurotransmitter release triggered by Ca influx through AMPA-type glutamate receptors
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DOI：
10.1038/nature05123
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发表时间：
2006-10-12
期刊：
影响因子：
64.8
通讯作者：
Diamond, Jeffrey S.
中科院分区：
文献类型：
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作者：
Chavez, Andres E.;Singer, Joshua H.;Diamond, Jeffrey S.
A17无长突细胞和视杆双极细胞（RBC）之间相互突触的反馈抑制塑造了视网膜中的光诱发反应（1-3）。谷氨酸介导的A17细胞兴奋激发GABA（γ-氨基丁酸）介导的对RBC的抑制反馈4 -6，但A17细胞树突释放GABA的机制尚不清楚。如果像在所有其他研究的突触中观察到的那样，电压门控钙通道（VGCC）将膜去极化与神经递质释放偶联（7），则前馈兴奋性突触后电位可以通过A17树突传播，在相邻突触处引发“环绕”反馈抑制性传递。然而，在这里，我们表明，GABA从大鼠视网膜A17细胞的释放不依赖于VGCC或膜去极化。相反，钙渗透性AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体（AMPAR），由红细胞释放的谷氨酸激活，提供触发GABA从A17细胞释放所需的钙流入。AMPAR介导的钙信号通过来自细胞内钙库的钙诱导钙释放（CICR）而放大。这些结果描述了一个快速的突触，独立于VGCC和膜去极化，并揭示了一个神经回路内的反馈抑制以前未知的形式。
Feedback inhibition at reciprocal synapses between A17 amacrine cells and rod bipolar cells (RBCs) shapes light-evoked responses in the retina(1-3). Glutamate-mediated excitation of A17 cells elicits GABA (gamma-aminobutyric acid)-mediated inhibitory feedback onto RBCs4-6, but the mechanisms that underlie GABA release from the dendrites of A17 cells are unknown. If, as observed at all other synapses studied, voltage-gated calcium channels (VGCCs) couple membrane depolarization to neurotransmitter release(7), feedforward excitatory postsynaptic potentials could spread through A17 dendrites to elicit 'surround' feedback inhibitory transmission at neighbouring synapses. Here we show, however, that GABA release from A17 cells in the rat retina does not depend on VGCCs or membrane depolarization. Instead, calcium-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs), activated by glutamate released from RBCs, provide the calcium influx necessary to trigger GABA release from A17 cells. The AMPAR-mediated calcium signal is amplified by calcium-induced calcium release (CICR) from intracellular calcium stores. These results describe a fast synapse that operates independently of VGCCs and membrane depolarization and reveal a previously unknown form of feedback inhibition within a neural circuit.