Nitric oxide disrupts Ca2+ homeostasis in hippocampal neurons.
Nitric oxide disrupts Ca2+ homeostasis in hippocampal neurons.
复制标题
一氧化氮破坏海马神经元的 Ca2 稳态。
DOI：
10.1046/j.1471-4159.1997.68010095.x
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发表时间：
1997
影响因子：
4.7
通讯作者：
Zhang,H
中科院分区：
文献类型：
--
作者：
Brorson,JR;Sulit,RA;Zhang,H
近年来，一氧化氮被认为是神经元毒性的重要介质，在许多情况下涉及细胞质Ca2+浓度的改变（[Ca2+]i）。在培养的海马神经元上的[Ca2+]荧光实验中，一氧化氮释放剂-亚硝基半胱氨酸在20分钟的暴露中产生延迟的[Ca2+]升高，这伴随着从去极化诱导的[Ca2+]瞬态恢复动力学的逐渐减慢。这些作用被氧化血红蛋白和超氧化物歧化酶阻断，证实了一氧化氮是负责任的因素，并表明它们与过氧亚硝酸盐的形成有关。线粒体ATP合酶抑制剂oligomycin也产生了类似的[Ca2+]稳态改变。在全细胞膜片钳- [Ca2+]联合荧光实验中，当ATP再生系统通过膜片移液器提供时，S -亚硝基半胱氨酸对静息[Ca2+]或直接去极化诱导的[Ca2+]瞬态恢复动力学没有影响。我们得出结论，长时间暴露于一氧化氮破坏[Ca2+]内稳态海马神经元通过损害Ca2+从细胞质中去除，可能是由于ATP消耗。由此产生的[Ca2+] imi的持续改变可能有助于延迟一氧化氮的神经毒性。
Nitric oxide has been recognized in recent years as an important mediator of neuronal toxicity, which in many cases involves alterations of the cytoplasmic Ca2+concentration ([Ca2+]i). In [Ca2+]ifluorimetric experiments on cultured hippocampal neurons, the nitric oxide‐releasing agentS‐nitrosocysteine produced a delayed rise in [Ca2+]iover a 20‐min exposure, which was accompanied by a progressive slowing of the kinetics of recovery from depolarization‐induced [Ca2+]itransients. These effects were blocked by oxyhemoglobin and by superoxide dismutase, confirming nitric oxide as the responsible agent, and suggesting that they involved peroxynitrite formation. Similar alterations of [Ca2+]ihomeostasis were produced by the mitochondrial ATP synthase inhibitor oligomycin, and when an ATP‐regenerating system was supplied via the patch pipette in combined whole‐cell patch‐clamp‐[Ca2+]ifluorimetry experiments,S‐nitrosocysteine had no effect on the resting [Ca2+]ior on the recovery kinetics of [Ca2+]itransients induced by direct depolarization. We conclude that prolonged exposure to nitric oxide disrupts [Ca2+]ihomeostasis in hippocampal neurons by impairing Ca2+removal from the cytoplasm, possibly as a result of ATP depletion. The resulting persistent alterations in [Ca2+]imay contribute to the delayed neurotoxicity of nitric oxide.