Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability
Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability
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DOI：
10.1016/s0028-3908(03)00047-9
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发表时间：
2003-04-01
影响因子：
4.7
通讯作者：
Lazdunski, M
中科院分区：
文献类型：
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作者：
Deval, E;Baron, A;Lazdunski, M
酸敏感离子通道3（ASIC 3）是由细胞外质子门控的阳离子通道。它在感觉神经元中高度表达，包括小的伤害感受神经元，并且已经提出参与与组织酸中毒相关的疼痛感知和机械感知。神经肽FF（NPFF）和FMRFamide已被证明可以增强来自培养的感觉神经元和酸敏感离子通道（ASIC）cDNA转染细胞的质子门控电流。在这项研究中，我们报告了另一种哺乳动物肽神经肽SF（NPSF），来自相同的前体，也大大增加了异源表达的ASIC 3的持续电流的幅度（12倍对FMRFamide和NPFF分别为19和9倍），EC 50接近50 μ M。在DRG神经元记录的内源性ASI3样持续电流上也观察到类似的效应，尽管幅度较小（NPSF、NPFF和FMRFamide分别增加2倍、3倍和7倍），并且基本上与失活速率的减慢有关。重要的是，这种调制诱导神经元兴奋性的变化，在细胞外酸化过程中施加的电刺激。因此，ASIC3介导的持续去极化及其通过神经肽的调节在调节多模态神经元兴奋性中可能是重要的，特别是在NPFF前体和ASIC3的表达水平增加的炎症条件下。(C)2003年爱思唯尔科学盖。All rights reserved.
Acid sensing ion channel 3 (ASIC3) is a cation channel gated by extracellular protons. It is highly expressed in sensory neurons, including small nociceptive neurons and has been proposed to participate in pain perception associated with tissue acidosis and in mechanoperception. Neuropeptide FF (NPFF) and FMRFamide have been shown to potentiate proton-gated currents from cultured sensory neurons and acid sensing ion channel (ASIC) cDNA transfected cells. In this study, we report that another mammalian peptide neuropeptide SF (NPSF), derived from the same precursor, also considerably increases the amplitude of the sustained current of heterologously expressed ASIC3 (12-fold vs. 19- and nine-fold for FMRFamide and NPFF, respectively) with an EC50 of similar to50 muM. Similar effects were also observed on endogenous ASI3-like sustained current recorded from DRG neurons although of smaller amplitudes (two-, three- and seven-fold increase for NPSF, NPFF and FMRFamide, respectively), and essentially related to a slowing down of the inactivation rate. Importantly, this modulation induced changes in neuronal excitability in response to an electrical stimulus applied during extracellular acidification. ASIC3-mediated sustained depolarisation, and its regulation by neuropeptides, could thus be important in regulating polymodal neuron excitability particularly under inflammatory conditions where the expression levels of both NPFF precursor and ASIC3 are increased. (C) 2003 Elsevier Science Lid. All rights reserved.