Kim Mean-Hwan, Uehara Shunsuke, Muroyama Akiko, Hille Bertil, Moriyama Yoshinori, Koh Duk-Su
Department of Physics, Pohang University of Science and Technology, Kyungbuk 790-784, Republic of Korea.
J Neurosci. 2008 Oct 22;28(43):10852-63. doi: 10.1523/JNEUROSCI.0894-08.2008.
Glutamate transporters are expressed throughout the CNS where their major role is to clear released glutamate from presynaptic terminals. Here, we report a novel function of the transporter in rat pinealocytes. This electrogenic transporter conducted inward current in response to L-glutamate and L- or D-aspartate and depolarized the membrane in patch-clamp experiments. Ca2+ imaging demonstrated that the transporter-mediated depolarization induced a significant Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ rise finally evoked glutamate exocytosis as detected by carbon-fiber amperometry and by HPLC. In pineal slices with densely packed pinealocytes, glutamate released from the cells effectively activated glutamate transporters in neighboring cells. The Ca2+ signal generated by KCl depolarization or acetylcholine propagated through several cell layers by virtue of the regenerative "glutamate-induced glutamate release." Therefore, we suggest that glutamate transporters mediate synchronized elevation of L-glutamate and thereby efficiently downregulate melatonin secretion via previously identified inhibitory metabotropic glutamate receptors in the pineal gland.
谷氨酸转运体在整个中枢神经系统中均有表达，其主要作用是清除突触前终末释放的谷氨酸。在此，我们报道了该转运体在大鼠松果体细胞中的一种新功能。这种生电转运体在膜片钳实验中对L-谷氨酸、L-或D-天冬氨酸产生内向电流，并使膜去极化。Ca²⁺成像显示，该转运体介导的去极化通过电压门控Ca²⁺通道诱导了显著的Ca²⁺内流。如通过碳纤维安培法和高效液相色谱法检测到的，Ca²⁺升高最终引发了谷氨酸的胞吐作用。在松果体细胞密集排列的松果体切片中，细胞释放的谷氨酸有效地激活了相邻细胞中的谷氨酸转运体。由氯化钾去极化或乙酰胆碱产生的Ca²⁺信号借助“谷氨酸诱导的谷氨酸释放”的再生特性在几个细胞层中传播。因此，我们认为谷氨酸转运体介导L-谷氨酸的同步升高，从而通过松果体中先前鉴定的抑制性代谢型谷氨酸受体有效地下调褪黑素分泌。
