Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons.
Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons.
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DOI：
10.1186/1744-8069-9-4
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发表时间：
2013-02-18
期刊：
影响因子：
3.3
通讯作者：
Xu GY
中科院分区：
文献类型：
--
作者：
Feng X;Zhou YL;Meng X;Qi FH;Chen W;Jiang X;Xu GY
硫化氢（H2S）是一种内源性气体递质/调节剂，它参与了包括炎症和伤害感受在内的多种过程。然而，H2S在三叉神经节（TG）神经元伤害性感受过程中的作用和机制尚不清楚。本研究旨在探讨内源性H2S合成酶胱硫醚-β-合成酶（cystathietrin-β-synthetase，CBS）在TG神经元中的分布及H2S对兴奋性和电压门控性钾通道的作用。进行免疫荧光研究以确定CBS是否在Kv1.1或Kv1.4阳性TG神经元中共表达。对来自成年雄性Sprague道利大鼠（6-8周龄）的急性分离的TG神经元进行全细胞膜片钳记录。用von Frey细丝检测大鼠注射硫氢化钠后的疼痛行为反应。在大鼠TG中，77.3±6.6%的神经元为CBS免疫反应阳性，85.1±3.8%为Kv1.1，97.8±1.1%为Kv1.4。双染显示CBS标记的细胞均为Kv1.1和Kv1.4阳性，但仅92.2±6.1%和78.2±9.9%的Kv1.1和Kv1.4阳性细胞含有CBS。应用H2S供体NaHS（250 μM）导致TG神经元记录的静息膜电位显著去极化。NaHS应用还导致基强度显著降低，动作电位阈值超极化，以及在2X和3X基强度刺激下诱发的动作电位数量显著增加。在电压钳条件下，TG神经元表现出短暂的A型（IA）和持续的外向整流钾电流（IK）。应用NaHS可抑制TG神经元的IK密度，而不改变IA密度（n=6）。此外，NaHS，硫化氢的供体，产生了剂量依赖性的方式在逃逸阈值的显着降低。这些数据表明，内源性H2S生成酶CBS与Kv1.1和Kv1.4在TG神经元中共定位良好，并且H2S产生机械性疼痛并增加神经元兴奋性，这可能在很大程度上通过抑制IK密度来介导，从而首次确定了TG疼痛和敏化的特定分子机制。
Hydrogen sulfide (H2S), an endogenous gaseotransmitter/modulator, is becoming appreciated that it may be involved in a wide variety of processes including inflammation and nociception. However, the role and mechanism for H2S in nociceptive processing in trigeminal ganglion (TG) neuron remains unknown. The aim of this study is to investigate distribution of endogenous H2S synthesizing enzyme cystathionine-β-synthetase (CBS) expression and role of H2S on excitability and voltage-gated potassium channels of TG neurons. Immunofluorescence studies were carried out to determine whether CBS was co-expressed in Kv1.1 or Kv1.4-positive TG neurons. Whole cell patch clamp recordings were employed on acutely isolated TG neurons from adult male Sprague Dawley rats (6–8 week old). von Frey filaments were used to examine the pain behavioral responses in rats following injection of sodium hydrosulfide. In rat TG, 77.3±6.6% neurons were immunoreactive for CBS, 85.1±3.8% for Kv1.1 and 97.8±1.1% for Kv1.4. Double staining showed that all CBS labeled cells were Kv1.1 and Kv1.4 positive, but only 92.2±6.1% of Kv1.1 and 78.2±9.9% of Kv1.4 positive cells contained CBS. Application of H2S donor NaHS (250 μM) led to a significant depolarization of resting membrane potential recorded from TG neurons. NaHS application also resulted in a dramatic reduction in rheobase, hyperpolarization of action potential threshold, and a significant increase in the number of action potentials evoked at 2X and 3X rheobase stimulation. Under voltage-clamp conditions, TG neurons exhibited transient A-type (IA) and sustained outward rectifier K+ currents (IK). Application of NaHS did suppress IK density while did not change IA density of TG neurons (n=6). Furthermore, NaHS, a donor of hydrogen sulfide, produced a significant reduction in escape threshold in a dose dependent manner. These data suggest that endogenous H2S generating enzyme CBS was co-localized well with Kv1.1 and Kv1.4 in TG neurons and that H2S produces the mechanic pain and increases neuronal excitability, which might be largely mediated by suppressing IK density, thus identifying for the first time a specific molecular mechanism underlying pain and sensitization in TG.
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