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首页> 外文期刊>Journal of Neurophysiology >Nitric oxide activates leak K+ currents in the presumed cholinergic neuron of basal forebrain.
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Nitric oxide activates leak K+ currents in the presumed cholinergic neuron of basal forebrain.

机译：一氧化氮激活基底前脑的推测胆碱能神经元中的泄漏K +电流。

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摘要

Learning and memory are critically dependent on basal forebrain cholinergic (BFC) neuron excitability, which is modulated profoundly by leak K(+) channels. Many neuromodulators closing leak K(+) channels have been reported, whereas their endogenous opener remained unknown. We here demonstrate that nitric oxide (NO) can be the endogenous opener of leak K(+) channels in the presumed BFC neurons. Bath application of 1 mM S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, induced a long-lasting hyperpolarization, which was often interrupted by a transient depolarization. Soluble guanylyl cyclase inhibitors prevented SNAP from inducing hyperpolarization but allowed SNAP to cause depolarization, whereas bath application of 0.2 mM 8-bromoguanosine-3',5'-cyclomonophosphate (8-Br-cGMP) induced a similar long-lasting hyperpolarization alone. These observations indicate that the SNAP-induced hyperpolarization and depolarization are mediated by the cGMP-dependent and -independent processes, respectively. When examined with the ramp command pulse applied at -70 mV under the voltage-clamp condition, 8-Br-cGMP application induced the outward current that reversed at K(+) equilibrium potential (E(K)) and displayed Goldman-Hodgkin-Katz rectification, indicating the involvement of voltage-independent K(+) current. By contrast, SNAP application in the presumed BFC neurons either dialyzed with the GTP-free internal solution or in the presence of 10 muM Rp-8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate sodium salt, a protein kinase G (PKG) inhibitor, induced the inward current that reversed at potentials much more negative than E(K) and close to the reversal potential of Na(+)-K(+) pump current. These observations strongly suggest that NO activates leak K(+) channels through cGMP-PKG-dependent pathway to markedly decrease the excitability in BFC neurons, while NO simultaneously causes depolarization by the inhibition of Na(+)-K(+) pump through ATP depletion.
机译：学习和记忆至关重要地取决于基底前脑胆碱能（BFC）神经元的兴奋性，该兴奋性受到泄漏K（+）通道的深刻调节。已经报道了许多关闭泄漏K（+）通道的神经调节剂，但它们的内源性开放剂仍然未知。我们在这里证明一氧化氮（NO）可能是假定的BFC神经元中泄漏K（+）通道的内源性开放剂。 1 mM S-亚硝基-N-乙酰青霉胺（SNAP）（一种NO供体）在浴中的应用导致了持久的超极化，该极化通常被瞬态去极化打断。可溶性鸟苷基环化酶抑制剂阻止SNAP诱导超极化，但允许SNAP引起去极化，而0.2 mM 8-溴鸟苷3'，5'-环一磷酸（8-Br-cGMP）的浴应用则单独导致了类似的持久超极化。这些观察结果表明，SNAP诱导的超极化和去极化分别由cGMP依赖性和非依赖性过程介导。当在电压钳制条件下使用在-70 mV处施加的斜坡命令脉冲进行检查时，使用8-Br-cGMP施加的外向电流在K（+）平衡电位（E（K））处反向，并显示出Goldman-Hodgkin- Katz整流，表明与电压无关的K（+）电流的参与。相比之下，SNAP在无BTP的内部溶液中透析或在存在10μMRp-8-溴-β-苯基-1，N（2）-乙鸟嘌呤3'，5'-环状单磷酸硫代磷酸钠盐，一种蛋白激酶G（PKG）抑制剂，诱导了内向电流的反向电势比E（K）负得多，并且接近Na（+）-K（+）泵浦电流的反向电势。这些观察结果强烈表明，NO通过cGMP-PKG依赖性途径激活泄漏K（+）通道，从而显着降低BFC神经元的兴奋性，而NO同时通过抑制Na（+）-K（+）泵通过ATP引起去极化。消耗。

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