期刊文献

Acid modulation of tetrodotoxin-resistant Na+ channels in rat nociceptive neurons 收藏

大鼠伤害性神经元酸调制抗毒素抗性Na + 通道
原文求助 发布源
作者
Michiko Nakamura[a]; Il-Sung Jang[a][b]
作者单位
[a] Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea [b] Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea
关键词
Acidosis; Inflammatory pain; TTX-R Na+ channels; Trigeminal ganglia; Patch clamp
关键词译文
酸度;炎症疼痛; TTX-R NA + 通道;三叉甘族;补丁夹
发布日期
28 November 2014
页码
82–89
DOI
10.1016/j.neuropharm.2014.11.005
来源信息
Neuropharmacology ISSN：0028-3908, 2015年, 90卷, 82–89页
摘要
Under pathological conditions including inflammation, ischemia and incision, extracellular pH falls down as low as 5.4. Although some mediators play pivotal roles in the development and maintenance of inflammatory hyperalgesia by affecting the functional properties of tetrodotoxin-resistant (TTX-R) Na+ channels, the roles of tissue acidosis in nociceptive transmission mediated by TTX-R Na+ channels are largely unknown. In the present study, we have investigated the effect of acidic pH on TTX-R Na+ currents (INa) in small-sized sensory neurons isolated from rat trigeminal ganglia using a whole-cell patch clamp technique. Acidic pH decreased the peak amplitude of TTX-R INa in a pH-dependent manner, but weak acid (≥pH 6.0) had a minor inhibitory effect on the TTX-R INa. Acidic pH also significantly shifted both the activation and steady-state fast inactivation relationships toward depolarized potentials. In addition, acidic pH had little effect on the use-dependent inhibition, and significantly retarded the development of inactivation and accelerated the recovery from inactivation of TTX-R Na+ channels. The results suggest that weak acid (≥pH 6.0) makes TTX-R Na+ channels to be suitable for the repetitive activation at depolarized membrane potentials. Given that both tissue acidosis and inflammatory mediators in inflamed or injured tissues act synergistically to promote nociceptive transmission by affecting the functional properties of TTX-R Na+ channels, these channels would be, at least in part, a good target to treat inflammatory pain.
摘要译文
在病理情况下，包括炎症，缺血和切口，外pH落下低至5.4。尽管一些介质通过影响河豚毒素抗性（TTX-R）钠\u003cSUP\u003e + \u003c/ SUP\u003e通道的功能特性起到炎性痛觉过敏的发展和维持关键作用，组织酸中毒在伤害性传输的作用介导的TTX-R娜\u003cSUP\u003e + \u003c/ SUP\u003e渠道在很大程度上是未知。在本研究中，我们使用的是全细胞膜片钳技术研究酸性pH值对TTX-R钠\u003cSUP\u003e + \u003c/ SUP\u003e电流（LuK）的效果在小型感觉神经元从大鼠三叉神经节隔离。酸性pH以pH依赖性的方式降低的TTX-R钠电流的峰值幅度，但是弱酸（≥pH6.0）对TTX-R钠电流轻微的抑制作用。酸性pH值也显著转移既激活和去极化对势稳态快速失活的关系。此外，酸性pH对使用依赖性抑制的影响不大，并显著延缓失活的发展，加速了恢复从TTX-R钠\u003cSUP\u003e + \u003c/ SUP\u003e通道的失活。结果表明，弱酸（≥pH6.0）使得TTX-R钠\u003cSUP\u003e + \u003c/ SUP\u003e通道适合于在去极化膜电位的重复激活。鉴于在发炎或受伤组织两者组织酸中毒和炎症介质协同作用通过影响TTX-R钠\u003cSUP\u003e + \u003c/ SUP\u003e通道的功能特性，以促进伤害性传输，这些信道会是这样，至少部分地，一个良好的目标治疗炎症性疼痛。
Michiko Nakamura[a]; Il-Sung Jang[a][b]. Acid modulation of tetrodotoxin-resistant Na+ channels in rat nociceptive neurons[J]. Neuropharmacology, 2015,90: 82–89