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感觉性肾神经支配:一种由于电压门控钠离子通道的独特表达模式而产生的肾脏特异性放电活动?

Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?

机构信息

Dept. of Medicine 4, Univ. of Erlangen-Nürnberg, Loschgestraβe 8, 91054 Erlangen, Germany.

出版信息

Am J Physiol Renal Physiol. 2013 Mar 1;304(5):F491-7. doi: 10.1152/ajprenal.00011.2012. Epub 2013 Jan 2.

Abstract

Sensory neurons with afferent axons from the kidney are extraordinary in their response to electrical stimulation. More than 50% exhibit a tonic firing pattern, i.e., sustained action potential firing throughout depolarizing, pointing to an increased excitability, whereas nonrenal neurons show mainly a phasic response, i.e., less than five action potentials. Here we investigated whether these peculiar firing characteristics of renal afferent neurons are due to differences in the expression of voltage-gated sodium channels (Navs). Dorsal root ganglion (DRG) neurons from rats (Th11-L2) were recorded by the current-clamp technique and distinguished as "tonic" or "phasic." In voltage-clamp recordings, Navs were characterized by their tetrodotoxoxin (TTX) sensitivity, and their molecular identity was revealed by RT-PCR. The firing pattern of 66 DRG neurons (41 renal and 25 nonrenal) was investigated. Renal neurons exhibited more often a tonic firing pattern (56.1 vs. 12%). Tonic neurons showed a more positive threshold (-21.75 ± 1.43 vs.-29.33 ± 1.63 mV; P < 0.05), a higher overshoot (56.74 [53.6-60.96] vs. 46.79 mV [38.63-54.75]; P < 0.05) and longer action potential duration (4.61 [4.15-5.85] vs. 3.35 ms [2.12-5.67]; P < 0.05). These findings point to an increased presence of the TTX-resistant Navs 1.8 and 1.9. Furthermore, tonic neurons exhibited a relatively higher portion of TTX-resistant sodium currents. Interestingly, mRNA expression of TTX-resistant sodium channels was significantly increased in renal, predominantly tonic, DRG neurons. Hence, under physiological conditions, renal sensory neurons exhibit predominantly a firing pattern associated with higher excitability. Our findings support that this is due to an increased expression and activation of TTX-resistant Navs.

摘要

肾脏传入轴突的感觉神经元在对电刺激的反应上非常特殊。超过 50%的神经元表现出紧张性放电模式,即持续的动作电位放电贯穿去极化,表明兴奋性增加,而非肾脏神经元主要表现出阶段性反应,即少于五个动作电位。在这里,我们研究了这些肾脏传入神经元特殊放电特征是否是由于电压门控钠离子通道 (Navs) 的表达差异所致。通过电流钳技术记录大鼠背根神经节 (DRG) 神经元,并将其区分成“紧张性”或“阶段性”。在电压钳记录中,Navs 的特征是对河豚毒素 (TTX) 的敏感性,通过 RT-PCR 揭示了它们的分子身份。研究了 66 个 DRG 神经元(41 个肾脏和 25 个非肾脏)的放电模式。肾脏神经元更常表现出紧张性放电模式(56.1%比 12%)。紧张性神经元的阈值更偏正(-21.75 ± 1.43 比-29.33 ± 1.63 mV;P < 0.05),超射更高(56.74 [53.6-60.96] 比 46.79 mV [38.63-54.75];P < 0.05),动作电位持续时间更长(4.61 [4.15-5.85] 比 3.35 ms [2.12-5.67];P < 0.05)。这些发现表明 TTX 抗性 Navs 1.8 和 1.9 的存在增加。此外,紧张性神经元表现出相对更高比例的 TTX 抗性钠电流。有趣的是,肾脏、主要是紧张性的 DRG 神经元中 TTX 抗性钠通道的 mRNA 表达显著增加。因此,在生理条件下,肾脏感觉神经元表现出与更高兴奋性相关的主要放电模式。我们的研究结果支持这是由于 TTX 抗性 Navs 的表达和激活增加所致。

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