一氧化氮对培养大鼠海马神经元L型钙通道的调控及其机制
发布时间：2018-08-14 17:47
【摘要】：一氧化氮(NO)是一种重要的信号转导分子,参与脑内许多生理和生理病理过程。大量证据表明伴随着缺氧和缺血的脑损伤,海马神经元会产生过量的NO。缺氧缺血时,离子跨膜重新分布,增加的钙内流能明显地影响NO合成酶的活性和产生NO的量,从而改变神经组织中的NO水平。然而,目前仍不清楚内源性的NO与引起钙内流的离子通道之间的关系。另外,对NO通过何种机制来介导钙内流也不十分清楚。L型钙通道在海马锥体神经元上分布很广,约30-50%的钙离子总电流来自L型钙通道。因此,调控L型钙通道的活动将显著影响钙离子的内流。 在本研究中,我们探讨了内源性一氧化氮对大鼠海马神经元L型钙通道的作用及其机制。当从钳制电位-50mV去极化至0mV时,NOS的底物L-精氨酸(L-Arg,1-3mM)增加了61%的L钙电流(n=30,p0.01)。另外,L-Arg使从-20mV到10mV的电流电压曲线(Ⅰ-Ⅴ)左移,说明这时的通道对去极化的电压变得更敏感。尼菲地平(NFDP)是二氢吡啶类的L型钙通道的阻断剂。20uMNFDP将L钙电流减少了60%(n=3,p0.05),L-Arg不再使剩余的电流增大,说明L-Arg的作用是通过L型钙通道起作用的。与L-Arg的作用相反,NOS的抑制剂N~G-Nitro-L-Arginine Methyl Ester(L-NAME,1-3mM)明显减少约51%的L钙电流(n=8,p0.01),提示在培养的海马神经元上一氧化氮(NO)对通道有基础调节。若预处理1mM L-NAME(n=16)和另一种nNOS抑制剂7-Nitroindazole(7-NINA,n=10),两者皆能部分阻断L-Arg对通道电流的增大作用(p0.05)。这些结果表明内源性的NO能使海马L型钙通道增强通道开放和提高其对电压的敏感性。 为了探测S-亚硝化是否参与介导内源性NO引起的通道活动,我们用N-ethylmaleimide (NEM,能二价修饰蛋白硫醇基团从而阻止进一步的S-亚硝
[Abstract]:Nitric oxide (NO) is an important signal transduction molecule involved in many physiological and pathophysiological processes in the brain. There is plenty of evidence that hippocampal neurons produce excess no with hypoxic and ischemic brain damage. During hypoxia-ischemia, the ion redistributes across the membrane, and the increased calcium influx can obviously affect the activity of no synthase and the amount of no produced, thus changing the level of no in nerve tissue. However, the relationship between endogenous no and ion channels causing calcium influx remains unclear. In addition, the mechanism of no mediated calcium influx is not very clear. L-type calcium channel is widely distributed in hippocampal pyramidal neurons, about 30-50% of the total calcium current comes from L-type calcium channel. Therefore, the regulation of L-type calcium channel activities will significantly affect the influx of calcium ions. In this study, we investigated the effect and mechanism of endogenous nitric oxide on L-type calcium channel in rat hippocampal neurons. L-arginine (L-Arginine 1-3mm), the substrate of 0mV, increased by 61% L Ca ~ (2 +) current (n ~ (30) p _ (0.01) when depolarization from clamp potential to -50 MV. In addition, L-Arg shifts the current voltage curve (鈪，
本文编号：2183633
[Abstract]:Nitric oxide (NO) is an important signal transduction molecule involved in many physiological and pathophysiological processes in the brain. There is plenty of evidence that hippocampal neurons produce excess no with hypoxic and ischemic brain damage. During hypoxia-ischemia, the ion redistributes across the membrane, and the increased calcium influx can obviously affect the activity of no synthase and the amount of no produced, thus changing the level of no in nerve tissue. However, the relationship between endogenous no and ion channels causing calcium influx remains unclear. In addition, the mechanism of no mediated calcium influx is not very clear. L-type calcium channel is widely distributed in hippocampal pyramidal neurons, about 30-50% of the total calcium current comes from L-type calcium channel. Therefore, the regulation of L-type calcium channel activities will significantly affect the influx of calcium ions. In this study, we investigated the effect and mechanism of endogenous nitric oxide on L-type calcium channel in rat hippocampal neurons. L-arginine (L-Arginine 1-3mm), the substrate of 0mV, increased by 61% L Ca ~ (2 +) current (n ~ (30) p _ (0.01) when depolarization from clamp potential to -50 MV. In addition, L-Arg shifts the current voltage curve (鈪，
本文编号：2183633
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