Mechanisms of Neurotransmitter Release in the Central Nervous System

为了研究脊椎动物中枢神经系统中的兴奋-递质释放偶联，使用从金鱼视网膜分离的ON型双极细胞，因为这些细胞具有非常大的突触前末端。同时监测细胞内游离Ca^<2+>浓度（[Ca^<2+]_i）和钙电流。由于递质的主要候选者是谷氨酸，因此递质的释放由对谷氨酸高度敏感的神经元进行电生理检测。Ca通道被鉴定为高电压激活的二氢吡啶敏感型，并且高度定位于突触前末梢。突触前末梢内[Ca^2+] i的基础水平是由Ca ^2+通过Ca^2+通道的渗漏内流和质膜Ca^2+泵的Ca^2+排出之间的平衡决定的。激活Ca^<2+>电流会诱发Ca^<2+>瞬变。其峰值水平似乎受内源性Ca^<2+>缓冲液的调节。由于Na^+/Ca^<2+>交换器和质膜上的Ca^<2 +>泵对Ca^<2+>的挤出作用，[Ca^<2+>] i升高后恢复到基础水平。激活二氢吡啶敏感的Ca^2+电流实际上诱发了谷氨酸样物质的释放。

To investigate the excitation-transmitter release coupling in the vertebrate central nervous system, ON-type bipolar cells dissociated from the goldfish retina were used because these cells have an extraordinarily large presynaptic terminal. The Ca current and the intracellular free Ca^<2+> concentration ([Ca^<2+>]_i) were simultaneously monitored. Since the leading candidate for the transmitter is glutamate, the transmitter release was detected electrophysiologically by the neuron, which was highly sensitive to glutamate.The Ca channel was identified as the high-voltage activated, dihydropyridine-sensitive type, and was highly localized to the presynaptic terminal. The basal level of [Ca^<2+>]_i in the presynaptic terminal was determined by a balance between the leakage influx of Ca^<2+> through Ca^<2+> channels and the extrusion of Ca^<2+> by the plasma membrane Ca^<2+> pump. Activation of the Ca^<2+> current evoked the Ca^<2+> transient. Its peak level seemed to be regulated by endogenous Ca^<2+> buffers. The increased [Ca^<2+>]_i recovered to the basal level due to the extrusion of Ca^<2+> by the Na^+/Ca^<2+> exchanger and the Ca^<2+> pump in the plasma membrane. Activation of the dihydropyridine-sensitive Ca^<2+> current in fact evoked the release of glutamate-like substance.