Laboratório de Eletrofisiologia, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza 60714-903, CE, Brazil.
Laboratório de Neurobiologia, Instituto de Ciências Biomédicas 1, Universidade de São Paulo, São Paulo 05508-000, SP, Brasil.
Int J Mol Sci. 2019 May 28;20(11):2611. doi: 10.3390/ijms20112611.
Melatonin is a neurohormone produced and secreted at night by pineal gland. Many effects of melatonin have already been described, for example: Activation of potassium channels in the suprachiasmatic nucleus and inhibition of excitability of a sub-population of neurons of the dorsal root ganglia (DRG). The DRG is described as a structure with several neuronal populations. One classification, based on the repolarizing phase of the action potential (AP), divides DRG neurons into two types: Without (N) and with (N) inflection on the repolarization phase of the action potential. We have previously demonstrated that melatonin inhibits excitability in N neurons, and in the present work, we aimed to investigate the melatonin effects on the other neurons (N) of the DRG neuronal population. This investigation was done using sharp microelectrode technique in the current clamp mode. Melatonin (0.01-1000.0 nM) showed inhibitory activity on neuronal excitability, which can be observed by the blockade of the AP and by the increase in rheobase. However, we observed that, while some neurons were sensitive to melatonin effect on excitability (excitability melatonin sensitive-EMS), other neurons were not sensitive to melatonin effect on excitability (excitability melatonin not sensitive-EMNS). Concerning the passive electrophysiological properties of the neurons, melatonin caused a hyperpolarization of the resting membrane potential in both cell types. Regarding the input resistance (R), melatonin did not change this parameter in the EMS cells, but increased its values in the EMNS cells. Melatonin also altered several AP parameters in EMS cells, the most conspicuously changed was the (dV/dt) of AP depolarization, which is in coherence with melatonin effects on excitability. Otherwise, in EMNS cells, melatonin (0.1-1000.0 nM) induced no alteration of (dV/dt) of AP depolarization. Thus, taking these data together, and the data of previous publication on melatonin effect on N neurons shows that this substance has a greater pharmacological potency on N neurons. We suggest that melatonin has important physiological function related to N neurons and this is likely to bear a potential relevant therapeutic use, since N neurons are related to nociception.
褪黑素是由松果体在夜间产生和分泌的神经激素。褪黑素的许多作用已经被描述过，例如：激活视交叉上核中的钾通道和抑制背根神经节（DRG）中神经元亚群的兴奋性。DRG 被描述为具有多个神经元群体的结构。一种分类方法是基于动作电位（AP）的复极化相，将 DRG 神经元分为两类：无（N）和有（N）AP 复极化相弯曲。我们之前已经证明褪黑素抑制 N 神经元的兴奋性，在本工作中，我们旨在研究褪黑素对 DRG 神经元群体中其他神经元（N）的影响。这项研究是使用在电流钳模式下的尖锐微电极技术进行的。褪黑素（0.01-1000.0 nM）对神经元兴奋性表现出抑制活性，这可以通过 AP 的阻断和阈强度的增加来观察到。然而，我们观察到，虽然一些神经元对褪黑素对兴奋性的作用敏感（兴奋性褪黑素敏感-EMS），但其他神经元对褪黑素对兴奋性的作用不敏感（兴奋性褪黑素不敏感-EMNS）。关于神经元的被动电生理特性，褪黑素使两种细胞类型的静息膜电位发生超极化。关于输入电阻（R），褪黑素在 EMS 细胞中没有改变这个参数，但增加了 EMNS 细胞中的值。褪黑素还改变了 EMS 细胞中几个 AP 参数，最明显的改变是 AP 去极化的（dV/dt），这与褪黑素对兴奋性的作用一致。否则，在 EMNS 细胞中，褪黑素（0.1-1000.0 nM）没有诱导 AP 去极化的（dV/dt）改变。因此，综合这些数据和之前关于褪黑素对 N 神经元作用的研究数据表明，这种物质对 N 神经元具有更大的药理学效力。我们认为褪黑素对 N 神经元具有重要的生理功能，这可能具有潜在的相关治疗用途，因为 N 神经元与疼痛感知有关。
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