Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type calcium currents in cones but not in rods
Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type calcium currents in cones but not in rods
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DOI：
10.1523/jneurosci.2735-04.2005
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发表时间：
2005-04-20
影响因子：
5.3
通讯作者：
Tachibana, M
中科院分区：
文献类型：
--
作者：
Hosoi, N;Arai, I;Tachibana, M
光感受器（视杆细胞和视锥细胞）的光反应通过位于视网膜外丛状层的突触传递到二级神经元（双极细胞和水平细胞）。虽然它已被很好地建立，突触后组III代谢型谷氨酸受体（mGluRs）的ON双极细胞有助于产生的ON信号，突触前的作用组III mGluRs仍有待阐明，在这个突触连接。我们通过将切片膜片钳技术应用于蝾螈视网膜来解决这个问题。OFF双极细胞和水平细胞在黑暗中产生稳定的内向电流，在光偏移时产生短暂的内向电流，这两者都是通过突触后非NMDA受体介导的。第三组mGluR特异性激动剂，L-2-氨基-4-膦酰基丁酸（L-AP-4），抑制稳态和关闭瞬态内向电流，但不影响谷氨酸诱导的电流在这些突触后神经元。L-AP-4通过将激活的电压依赖性转移到更正的膜电位来抑制视锥细胞中的突触前L型钙电流（I-Ca）。在视锥细胞膜电位的生理范围内，I-Ca的抑制作用最为显著。相反，L-AP-4不影响杆中的L型I-Ca。光感受器和突触连接的二级神经元的配对记录证实，L-AP-4抑制视锥细胞中的I-Ca和谷氨酸释放，但不抑制视杆细胞中的I-Ca和谷氨酸释放。此外，我们发现，exocytosed质子也抑制I-Ca在锥，但不是在杆。视锥细胞中I-Ca的选择性调节可能有助于通过控制视锥细胞释放递质的量来拓宽突触传递的动态范围。
Light responses of photoreceptors (rods and cones) are transmitted to the second-order neurons ( bipolar cells and horizontal cells) via glutamatergic synapses located in the outer plexiform layer of the retina. Although it has been well established that postsynaptic group III metabotropic glutamate receptors (mGluRs) of ON bipolar cells contribute to generating the ON signal, presynaptic roles of group III mGluRs remain to be elucidated at this synaptic connection. We addressed this issue by applying the slice patch-clamp technique to the newt retina. OFF bipolar cells and horizontal cells generate a steady inward current in the dark and a transient inward current at light offset, both of which are mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist, L-2-amino-4-phosphonobutyric acid (L-AP-4), inhibited both the steady and off-transient inward currents but did not affect the glutamate-induced current in these postsynaptic neurons. L-AP-4 inhibited the presynaptic L-type calcium current (I-Ca) in cones by shifting the voltage dependence of activation to more positive membrane potentials. The inhibition of I-Ca was most prominent around the physiological range of cone membrane potentials. In contrast, L-AP-4 did not affect L-type I-Ca in rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed that L-AP-4 inhibited both I-Ca and glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibited I-Ca in cones but not in rods. Selective modulation of I-Ca in cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.