Relationship between rat retinal degeneration and potassium channel KCNQ5 expression
Relationship between rat retinal degeneration and potassium channel KCNQ5 expression
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DOI：
10.1016/j.exer.2014.12.009
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发表时间：
2015-02-01
影响因子：
3.4
通讯作者：
Martinez-Galan, Juan R.
中科院分区：
文献类型：
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作者：
Caminos, Elena;Vaquero, Cecilia F.;Martinez-Galan, Juan R.
KCNQ5/Kv7.5是一个低阈值非失活的电压门控钾通道，优先靶向脑神经元的兴奋性末梢。猴视网膜色素上皮细胞和脑神经元中的m型电流是由KCNQ5通道亚基介导的。本研究分析了KCNQ5在正常大鼠视网膜和光感受器变性过程中的表达及其与其他蛋白的相互作用信号。采用免疫细胞化学和Western blot方法研究KCNQ5在正常大鼠视网膜（SD - Sprague-Dawley， SD）和P23H-1视网膜色素性视网膜炎模型中的表达谱。KCNQ5与钙调蛋白（CaM）、泡状谷氨酸转运蛋白1 （VGluT1）和胶质原纤维酸性蛋白（GFAP）的物理相互作用通过原位接近结联法分析，并通过钙记录进行支持。KCNQ5表达于视网膜色素上皮的丛状层、神经节细胞层和基膜。KCNQ5与CaM、VGluT1和GFAP的物理相互作用随年龄和视网膜变性而改变。KCNQ5/CaM相互作用在光感受器几乎完全消失时达到最大水平；随着变性的进展，内视网膜中KCNQ5/VGluT1相互作用信号减少，KCNQ5/GFAP相互作用信号增加。P23H-1星形胶质细胞和神经元的基础钙水平高于对照SD视网膜。本研究表明，KCNQ5存在于大鼠视网膜中，其活性可能受到CaM的调节。P23H-1大鼠视网膜变性的进展可能伴随着KCNQ5与CaM在原位系统中的相互作用。KCNQ5与VGluT1或GFAP之间的关系需要更谨慎的解释。(C) 2014年作者。Elsevier Ltd.出版。
KCNQ5/Kv7.5 is a low-threshold non-inactivating voltage-gated potassium channel preferentially targeted to excitatory endings in brain neurons. The M-type current is mediated by KCNQ5 channel subunits in monkey retinal pigment epithelium cells and in brain neurons. This study was undertaken to analyze KCNQ5 expression and the interaction signals of KCNQ5 with other proteins in normal rat retina and during photoreceptor degeneration. The KCNQ5 expression pattern was studied by immunocytochemistry and Western blot in normal rat retinas (Sprague-Dawley, SD) and P23H-1 rats as a retinitis pigmentosa model. The physical interactions of KCNQ5 with calmodulin (CaM), vesicular glutamate transporter 1 (VGluT1) and glial fibrillary acidic protein (GFAP) were analyzed by in situ proximity ligation assays and were supported by calcium recording. KCNQ5 expression was found in the plexiform layers, ganglion cell layer and basal membrane of the retinal pigment epithelium. The physical interactions among KCNQ5 and CaM, VGluT1 and GFAP changed with age and during retinal degeneration. The maximal level of KCNQ5/CaM interaction was found when photoreceptors had almost completely disappeared; the KCNQ5/VGluT1 interaction signal decreased and the KCNQ5/GFAP interaction increased in the inner retina, while degeneration progressed. The basal calcium levels in the astrocytes and neurons of P23H-1 were higher than in the control SD retinas. This study demonstrates that KCNQ5 is present in the rat retina where its activity may be moderated by CaM. Retinal degeneration progression in P23H-1 rats can be followed by an interaction between KCNQ5 with CaM in an in situ system. The relationship between KCNQ5 and VGluT1 or GFAP needs to be more cautiously interpreted. (C) 2014 The Authors. Published by Elsevier Ltd.