Modulation of voltage-gated Ca2+ channels in rat retinal ganglion cells by gabapentin.
Modulation of voltage-gated Ca2+ channels in rat retinal ganglion cells by gabapentin.
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DOI：
10.1017/s0952523813000588
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发表时间：
2014-01
影响因子：
1.9
通讯作者：
Barnes S
中科院分区：
文献类型：
--
作者：
Farrell SR;Sargoy A;Brecha NC;Barnes S
电压门控Ca2+通道α2δ辅助亚基是VGCC功能的重要调节剂。加巴喷丁与α2δ1和α2δ2亚基相互作用，据报道可降低Ca2+通道电流振幅（ICa）。本研究旨在确定加巴喷丁对视网膜神经节细胞（RGCs） vgcc的影响。使用全细胞膜片钳记录离体RGCs中的ICa，并使用钙显像原位测量RGCs中的Ca2+瞬态。采用免疫组化方法检测加巴喷丁预处理前后离体RGCs中含α2δ1的VGCCs的存在。与对照组相比，加巴喷丁急性给药减少了ICa和Ca2+瞬态。在离体rgc中，加巴喷丁预处理（4-18 h）降低了ICa，与未预处理的细胞相比，细胞表面α2δ1染色降低。经预处理的离体RGCs急性给予加巴喷丁进一步降低了ICa。这些结果表明，加巴喷丁具有降低离体rgc中ICa的短期和长期机制。一些Ca2+通道阻滞剂已被证明可以保护视网膜创伤中的RGCs，这表明加巴喷丁调节VGCCs可以防止创伤和疾病中RGCs中Ca2+水平升高的有害影响。
The α2δ auxiliary subunits of voltage-gated Ca2+ channels (VGCCs) are important modulators of VGCC function. Gabapentin interacts with α2δ1 and α2δ2 subunits and is reported to reduce Ca2+ channel current amplitude (ICa). This study aimed to determine the effects of gabapentin on VGCCs in retinal ganglion cells (RGCs). Whole cell patch clamp was used to record ICa in isolated RGCs, and calcium imaging was used to measure Ca2+ transients from RGCs in situ. Immunohistochemistry was used to detect the presence of α2δ1-containing VGCCs in isolated RGCs in the absence and presence of gabapentin pretreatment. Acute administration of gabapentin reduced ICa and Ca2+ transients compared to control conditions. In isolated RGCs, pretreatment with gabapentin (4–18 h) reduced ICa, and cell surface α2δ1 staining was reduced compared to nonpretreated cells. Acute administration of gabapentin to isolated RGCs that had been pretreated further reduced ICa. These results show that gabapentin has both short-term and long-term mechanisms to reduce ICa in isolated RGCs. Some Ca2+ channel blockers have been shown to protect RGCs in retinal trauma suggesting that modulation of VGCCs by gabapentin may prevent the deleterious effects of elevated Ca2+ levels in RGCs in trauma and disease.