Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system
Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system
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DOI：
10.1113/jphysiol.2002.030692
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发表时间：
2003-01-01
影响因子：
5.5
通讯作者：
Canessa, CM
中科院分区：
文献类型：
--
作者：
de la Rosa, DA;Krueger, SR;Canessa, CM
酸敏感离子通道ASIC 1是哺乳动物神经系统的质子门控离子通道。它在感觉神经元中的表达和低细胞外pH的激活表明ASIC参与传递由损伤或炎症引起的酸化产生的伤害性冲动。然而，ASIC1的表达并不局限于感觉神经元。为了了解ASIC 1在CNS中的功能作用，我们研究了其在其中的表达和亚细胞分布。特别是，我们研究了在生理条件下局部pH可能下降到足以激活ASIC1的区域中ASIC1的存在。特异性抗体免疫组化染色显示ASIC1广泛表达于成年大鼠大脑的许多区域，包括大脑皮层、海马和小脑。在细胞内，ASIC 1主要分布于整个索马和沿着轴突和树突的分支。ASIC1在pH可能达到低值的微区中不富集，例如在突触囊泡或突触膜中。在培养的海马神经元中，突触前或突触后ASIC1不受突触活动的门控。阻断或脱敏ASIC1与阿米洛利或PH 6.7，分别没有修改突触后电流。最后，小鼠大脑中ASIC1的个体发育显示，从胚胎第12天到出生后，ASIC1蛋白的表达水平恒定，这表明在大脑发育过程中，ASIC1的表达水平早期且几乎恒定。
The acid-sensitive ion channel ASIC1 is a proton-gated ion channel from the mammalian nervous system. Its expression in sensory neurons and activation by low extracellular pH suggest that ASIC is involved in transmitting nociceptive impulses produced by the acidification caused by injury or inflammation. However, ASIC1 expression is not restricted to sensory neurons. To understand the functional role of ASIC1 in the CNS we investigated its expression and subcellular distribution therein. In particular, we examined the presence of ASIC1 in domains where the local pH may drop sufficiently to activate ASIC1 under physiological conditions. Immunostaining with specific antibodies revealed broad expression of ASIC1 in many areas of the adult rat brain including the cerebral cortex, hippocampus and cerebellum. Within cells, ASIC1 was found predominantly throughout the soma and along the branches of axons and dendrites. ASIC1 was not enriched in the microdomains where pH may reach low values, such as in synaptic vesicles or synaptic membranes. Pre- or postsynaptic ASIC1 was not gated by synaptic activity in cultured hippocampal neurons. Blockage or desensitization of ASIC1 with amiloride or PH 6.7, respectively, did not modify postsynaptic currents. Finally, the ontogeny of ASIC1 in mouse brain revealed constant levels of expression of ASIC1 protein from embryonic day 12 to the postnatal period, indicating an early and almost constant level of expression of ASIC1 during brain development.