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首页> 外文期刊>The Journal of Physiology >Nitric oxide inhibits neuroendocrine Ca(V)1 L-channel gating via cGMP-dependent protein kinase in cell-attached patches of bovine chromaffin cells.
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Nitric oxide inhibits neuroendocrine Ca(V)1 L-channel gating via cGMP-dependent protein kinase in cell-attached patches of bovine chromaffin cells.

机译：一氧化氮通过牛嗜铬细胞的细胞贴片中的cGMP依赖性蛋白激酶抑制神经内分泌Ca（V）1 L通道门控。

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Nitric oxide (NO) regulates the release of catecholamines from the adrenal medulla but the molecular targets of its action are not yet well identified. Here we show that the NO donor sodium nitroprusside (SNP, 200 &mgr;M) causes a marked depression of the single Ca(V)1 L-channel activity in cell-attached patches of bovine chromaffin cells. SNP action was complete within 3-5 min of cell superfusion. In multichannel patches the open probability (NP(o)) decreased by ~60 % between 0 and +20 mV. Averaged currents over a number of traces were proportionally reduced and showed no drastic changes to their time course. In single-channel patches the open probability (P(o)) at +10 mV decreased by the same amount as that of multichannel patches (~61 %). Such a reduction was mainly associated with an increased probability of null sweeps and a prolongation of mean shut times, while first latency, mean open time and single-channel conductance were not significantly affected. Addition of the NO scavenger carboxy-PTIO or cell treatment with the guanylate cyclase inhibitor ODQ prevented the SNP-induced inhibition. 8-Bromo-cyclicGMP (8-Br-cGMP; 400 &mgr;M) mimicked the action of the NO donor and the protein kinase G blocker KT-5823 prevented this effect. The depressive action of SNP was preserved after blocking the cAMP-dependent up-regulatory pathway with the protein kinase A inhibitor H89. Similarly, the inhibitory action of 8-Br-cGMP proceeded regardless of the elevation of cAMP levels, suggesting that cGMP/PKG and cAMP/PKA act independently on L-channel gating. The inhibitory action of 8-Br-cGMP was also independent of the G protein-induced inhibition of L-channels mediated by purinergic and opiodergic autoreceptors. Since Ca(2+) channels contribute critically to both the local production of NO and catecholamine release, the NO/PKG-mediated inhibition of neuroendocrine L-channels described here may represent an important autocrine signalling mechanism for controlling the rate of neurotransmitter release from adrenal glands.
机译：一氧化氮（NO）调节儿茶酚胺从肾上腺髓质的释放，但尚未明确确定其作用的分子靶标。在这里，我们显示NO供体硝普钠（SNP，200μM）引起牛嗜铬细胞的细胞贴片中单个Ca（V）1 L通道活性的明显降低。 SNP作用在细胞融合后3-5分钟内完成。在多通道补丁中，打开概率（NP（o））在0至+20 mV之间降低了〜60％。多条迹线上的平均电流成比例地减小，并且在时间上没有明显变化。在单通道补丁中，+ 10 mV时的打开概率（P（o））降低的程度与多通道补丁的开启概率（〜61％）相同。这种减少主要与无效扫描的可能性增加和平均关闭时间的延长有关，而第一次等待时间，平均打开时间和单通道电导没有受到显着影响。 NO清除剂羧基-PTIO的添加或鸟苷酸环化酶抑制剂ODQ的细胞处理阻止了SNP诱导的抑制。 8-Bromo-cyclicGMP（8-Br-cGMP; 400μM）模仿了NO供体的作用，蛋白激酶G阻滞剂KT-5823阻止了这种作用。用蛋白激酶A抑制剂H89阻断cAMP依赖性上调途径后，SNP的抑制作用得以保留。同样，无论cAMP水平升高如何，都进行8-Br-cGMP的抑制作用，这表明cGMP / PKG和cAMP / PKA独立作用于L通道门控。 8-Br-cGMP的抑制作用也独立于嘌呤能和视蛋白能自身受体介导的G蛋白诱导的L通道抑制。由于Ca（2+）通道对当地的NO和儿茶酚胺释放均起关键作用，因此，此处描述的NO / PKG介导的神经内分泌L通道抑制作用可能代表着重要的自分泌信号传导机制，可控制从肾上腺释放神经递质的速率腺体。

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