Direct actions of nitric oxide on rat neurohypophysial K+ channels
Direct actions of nitric oxide on rat neurohypophysial K+ channels
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DOI：
10.1111/j.1469-7793.1999.00165.x
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发表时间：
1999-10-01
影响因子：
5.5
通讯作者：
Jackson, MB
中科院分区：
文献类型：
--
作者：
Ahern, GP;Hsu, SF;Jackson, MB
1.一氧化氮（NO）已被证明可以调节垂体后叶神经肽的分泌。本研究表明，NO激活垂体后叶神经末梢的大电导钙激活钾通道（BK）.无论是笼状NO的光解或与化学供体产生的NO，不可逆地增强了由于BK通道的全末端K+电流的组件，并增加了BK通道的活动在离体补丁。NO也抑制瞬态A电流。这些作用的时间过程是非常不同的，BK通道激活在几分钟内缓慢发展，而A-电流的抑制紧随NO的解除.在鸟苷酸环化酶抑制剂存在的情况下以及从移液器溶液中去除ATP或GTP后，NO激活BK通道，这表明了cGMP非依赖性信号通路。巯基烷基化剂N-乙基马来酰亚胺（NEM）增加BK通道活性。NEM预处理阻断NO激活. BK通道的NO激活独立于电压和胞浆Ca ~（2+）浓度。此外，NO消除了通道激活的严格的Ca 2+要求，使通道即使在纳摩尔Ca 2+水平下也高度活跃。这些结果表明，NO，或活性氮的副产物，化学修饰神经末梢BK通道或密切相关的蛋白质，从而产生通道活性的增加。这种激活可能抑制垂体后叶神经末梢的冲动活动，这可能解释了NO对分泌的抑制作用。
1. Nitric oxide (NO) has been shown to modulate neuropeptide secretion from the posterior pituitary. Here we show that NO activates large-conductance Ca2+-activated K+ (BK) channels in posterior pituitary nerve terminals.2. NO, generated either hy the photolysis of caged-NO or with chemical donors, irreversibly enhanced the component of whole-terminal K+ current due to BK channels and increased the activity of BK channels in excised patches. NO also inhibited the transient A-current. The time courses of these effects on K+ current were very different; activation of BK channels developed slowly over several minutes whereas inhibition of A-current immediately followed NO uncaging.3. Activation of BK channels by NO occurred in the presence of guanylyl cyclase inhibitors and after removal of ATP or GTP from the pipette solution, suggesting a cGMP-independent signalling pathway.4. The sulfhydryl alkylating agent N-ethyl maleimide (NEM) increased BK channel activity. Pretreatment with NEM occluded NO activation.5. NO activation of BK channels occurred independently of voltage and cytoplasmic Ca2+ concentration. In addition, NO removed the strict Ca2+ requirement for channel activation, rendering channels highly active even at nanomolar Ca2+ levels.6. These results suggest that NO, or a reactive nitrogen byproduct, chemically modifies nerve terminal BK channels or a closely associated protein and thereby produces an increase in channel activity. Such activation is likely to inhibit impulse activity in posterior pituitary nerve terminals and this may explain the inhibitory action of NO on secretion.