Département de Pédiatrie, Centre de Recherche de l'Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, Québec, QC, Canada.
Department of Neuroscience and Physiology and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY, USA.
Exp Physiol. 2019 Apr;104(4):463-468. doi: 10.1113/EP087461. Epub 2019 Feb 27.
What is the central question of the study? Progesterone is considered a respiratory stimulant drug, but its effect on medullary respiratory neurons are poorly documented. We investigated whether progesterone alters spontaneous activity of neurons in the nucleus of the solitary tract (NTS). What is the main finding and its importance? In NTS neurons, progesterone decreases the action potential firing frequency in response to current injections and the amplitude of excitatory postsynaptic currents. Based on the established neuroprotective effect of progesterone against excitotoxicity resulting from insults, this inhibitory effect is likely to reflect inhibition of ion fluxes. These results are important because they further our understanding of the mechanisms underlying the diversity of respiratory effects of progesterone.
Progesterone is known to stimulate breathing, but its actions on the respiratory control system have received limited attention. We addressed this issue at the cellular level by testing the hypothesis that progesterone augments excitatory currents at the level of the nucleus tractus solitarii (NTS). Medullary slices from juvenile male rats (14-17 days of age) containing the commissural region of the NTS (NTScom) were incubated with progesterone (1 μm) or vehicle (0.004% DMSO) for 60 min. We performed whole-cell voltage-clamp recordings of spontaneous excitatory postsynaptic currents (EPSCs) in the NTScom and determined membrane properties by applying depolarizing current steps. In comparison to vehicle-treated cells, progesterone exposure attenuates the firing frequency response to current injection and reduces the EPSC amplitude without modifying the EPSC frequency or the basal membrane properties. These data do not support our hypothesis, because they indicate that incubation with progesterone attenuates intrinsic action potential generation and inhibits excitatory synaptic inputs in the NTS. Given that these results are more in line with the protective effect of progesterone against excitotoxicity resulting from various insults, we propose that progesterone acts via inhibition of ionic flux.
研究的核心问题是什么？孕激素被认为是一种呼吸兴奋剂，但关于其对延髓呼吸神经元影响的记录很少。我们研究了孕激素是否会改变孤束核（NTS）神经元的自发性活动。主要发现及其重要性是什么？在 NTS 神经元中，孕激素降低了对电流注入的动作电位放电频率和兴奋性突触后电流的幅度。基于孕激素对兴奋性毒性引起的损伤的已建立的神经保护作用，这种抑制作用可能反映了离子流的抑制。这些结果很重要，因为它们进一步了解了孕激素对呼吸作用多样性的潜在机制。
孕激素已知可刺激呼吸，但对呼吸控制系统的作用却受到了限制。我们通过测试孕激素增强孤束核（NTS）水平兴奋性电流的假设来解决这个问题。来自 14-17 天大的雄性幼鼠的延髓切片（包含 NTS 的连合区（NTScom））用孕激素（1 μm）或载体（0.004% DMSO）孵育 60 分钟。我们在 NTScom 中进行了自发性兴奋性突触后电流（EPSC）的全细胞膜片钳记录，并通过施加去极化电流步来确定膜特性。与载体处理的细胞相比，孕激素暴露会降低对电流注入的放电频率反应，并减小 EPSC 幅度，而不改变 EPSC 频率或基础膜特性。这些数据不支持我们的假设，因为它们表明孕激素孵育会减弱内在动作电位的产生并抑制 NTS 中的兴奋性突触输入。鉴于这些结果更符合孕激素对各种损伤引起的兴奋性毒性的保护作用，我们提出孕激素通过抑制离子流起作用。
