Nitric Oxide Acts as a Volume Transmitter to Modulate Electrical Properties of Spontaneously Firing Neurons via Apamin-Sensitive Potassium Channels
Nitric Oxide Acts as a Volume Transmitter to Modulate Electrical Properties of Spontaneously Firing Neurons via Apamin-Sensitive Potassium Channels
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DOI：
10.1523/jneurosci.4511-09.2010
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发表时间：
2010-02-03
影响因子：
5.3
通讯作者：
Rehder, Vincent
中科院分区：
文献类型：
--
作者：
Artinian, Liana;Tornieri, Karine;Rehder, Vincent
一氧化氮 (NO) 是一种自由基和气体，其特性使一氧化氮能够通过膜扩散，并有可能使其发挥“体积信使”的作用。这项研究有两个目标：首先，研究 NO 作为神经元兴奋性调节剂的机制；其次，比较化学 NO 供体释放 NO 产生的 NO 效应与单个神经元释放生理 NO 引起的 NO 效应。我们证明，NO 可以使软体动物 Helisoma trivolvis 的 B5 神经元的膜电位去极化，最初增加其放电率，随后导致神经元沉默。 NO 的两种作用都是通过抑制 Ca 激活的伊比利亚毒素和 apamin 敏感 K 通道介导的，但只有对 apamin 敏感 K 通道的抑制完全模拟了 NO 对放电活动的所有影响，表明 NO 的大部分电效应是通过抑制 apamin 敏感 K 通道介导的。我们进一步表明，单个神经元释放足够量的 NO 来影响附近 B5 神经元的电活动。这些效应与化学 NO 供体 NOC-7 [3-(2-羟基-1-甲基-2-亚硝基肼基)-N-甲基-1-丙胺] 释放的 NO 类似，验证了 NO 供体在神经元兴奋性研究中的使用。与先前证明NO在神经突生长和生长锥运动中的作用的研究结果一起，结果表明NO有可能通过调节位于NO生成细胞附近的神经元的电活动和神经突生长来塑造神经系统的发育，支持NO作为体积信使的概念。
Nitric oxide (NO) is a radical and a gas, properties that allow NO to diffuse through membranes and potentially enable it to function as a "volume messenger." This study had two goals: first, to investigate the mechanisms by which NO functions as a modulator of neuronal excitability, and second, to compare NO effects produced by NO release from chemical NO donors with those elicited by physiological NO release from single neurons. We demonstrate that NO depolarizes the membrane potential of B5 neurons of the mollusk Helisoma trivolvis, initially increasing their firing rate and later causing neuronal silencing. Both effects of NO were mediated by inhibition of Ca-activated iberiotoxin-and apamin-sensitive K channels, but only inhibition of apamin-sensitive K channels fully mimicked all effects of NO on firing activity, suggesting that the majority of electrical effects of NO are mediated via inhibition of apamin-sensitive K channels. We further show that single neurons release sufficient amounts of NO to affect the electrical activity of B5 neurons located nearby. These effects are similar to NO release from the chemical NO donor NOC-7 [3-(2-hydroxy-1-methyl-2-nitrosohydazino)-N-methyl-1-propyanamine], validating the use of NO donors in studies of neuronal excitability. Together with previous findings demonstrating a role for NO in neurite outgrowth and growth cone motility, the results suggest that NO has the potential to shape the development of the nervous system by modulating both electrical activity and neurite outgrowth in neurons located in the vicinity of NO-producing cells, supporting the notion of NO functioning as a volume messenger.