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Na+,K+-ATP酶参与缺氧所致大鼠皮质神经元内钙升高
李石,郭芳,董惠,王永利
0
(河北医科大学药理学教研室,石家庄,050017;河北医科大学第二医院神经内科,石家庄,050017)
摘要:
目的:探讨Na+,K+-ATP酶对缺氧所致大鼠皮质神经元内钙升高的影响.方法:采用激光共聚焦显微镜及可视化动缘探测系统,测定培养大鼠皮质神经元在缺氧不同时间和双氢哇巴因(DHO,一种Na+-K+-ATP酶抑制剂)不同浓度时细胞内钙离子浓度([Ca2+]i)和细胞内钠离子浓度([Na+]i),并观察DHO对缺氧后神经元[Ca2+]i和[Na+]i升高作用的影响.结果:DHO(10-9~10-3mol/L)和缺氧(4~20 min)均可显著升高正常皮质神经元[Ca2+]i和[Na+]i,并分别具有剂量依赖性和时间依赖性.在缺氧4 min时皮质神经元[Ca2+]i和[Na+]i即明显升高,此时给予DHO 10-3mol/L可使二者进一步升高;但当皮质神经元缺氧15 min后,再给予相同剂量的DHO则不能使[Ca2+]i和[Na+]i进一步增加;若对DHO(10-3mol/L)预先升高[Ca2+]i的正常神经元再进行缺氧灌流,则[Ca2+]i不继续升高.结论: Na+,K+-ATP酶抑制是缺氧所致大鼠皮质神经元[Ca2+]i升高的机制之一.
关键词:  Na+,K+-ATP酶、神经元、缺氧
DOI:10.3724/SP.J.1008.2007.00044
投稿时间:2006-08-24修订日期:2006-11-24
基金项目:
Involvement of Na+,K+-ATPase in hypoxia-induced increase of cytosolic Ca2+ in rat cortical neurons
LI Shi,GUO Fang,DONG Hui,WANG Yong-li
(河北医科大学药理学教研室,石家庄,050017)
Abstract:
Objective:To investigate the effect of Na^+,K^+-ATPase on the increase of cytosolic Ca^2+ level induced by hypoxia in rat cortical neurons. Methods: Using confocal laser scanning microscope and video based motion edge detection system, we measured the intraeellular Ca^2+ concentration ([Ca2+]i ) and Na^+ concentration ([Na^-]i ) in cortical neurons exposed to hypoxia for different time periods and at presence of different concentrations of dihydroouabain (DHO, an inhibitor of Na^+,K^+-ATPase ). We also observed the effect ofNa^+,K^+-ATPase on the increase of cytosolic Ca^2+ level induced by hypoxia in rat cortical neurons. Results: DHO (10^-9-10^-3mol/L) dose-dependently and hypoxia(4-20 min) time-dependently increased the levels of [Ca^2+] and [Na^+] in cultured cortical neurons. [Ca^2+]i and [Na^+]i increased significantly 4 min after cortical neurons were exposed to hypoxia, and addition of DHO ( 10^-3mol/L) further increased their concentrations. While 15 min after hypoxia exposure, different concentrations of DHO did not further increase [Ca^2+] and [Na^+]i We also found that hypoxia exposure did not enhance DHO pretreatment-induced [Ca^2+]i increase. Couclusion: Inhibition of Na^+,K^+-ATPase activity is one of the mechanisms responsible for hypoxia-induced elevation of [Ca2+]i in cortical neurons.
Key words:  Na^+,K^+-ATPase  neurons  anoxia