Department of Chemistry and Biochemistry, Centre of Chemistry and Biochemistry, Faculty of Sciences University of Lisbon, Lisbon, Portugal.
Department of Physiology, Nova Medical School/Faculdade de Ciências Médicas, Lisbon, Portugal.
Eur J Neurosci. 2019 Jun;49(11):1418-1435. doi: 10.1111/ejn.14331. Epub 2019 Jan 27.
The function of hippocampus as a hub for energy balance is a subject of broad and current interest. This study aims at providing more evidence on this regard by addressing the effects of feeding cycle on the voltage-gated sodium (Na ) currents of acutely isolated Wistar rat hippocampal CA1 neurones. Specifically, by applying patch clamp techniques (whole cell voltage clamp and single channel in inside-out patches) we assessed the influence of feeding and fasting conditions on the intrinsic biophysical properties of Na currents. Additionally, mass spectrometry and western blotting experiments were used to address the effect of feeding cycle over the Na channel population of the rat hippocampus. Na currents were recorded in neurones obtained from fed and fasted animals (here termed "fed neurones" and "fasted neurones", respectively). Whole cell Na currents of fed neurones, as compared to fasted neurones, showed increased mean maximum current density and a higher "window current" amplitude. We demonstrate that these results are supported by an increased single channel Na conductance in fed neurones and, also, by a greater Nav1.2 channel density in plasma membrane-enriched fractions of fed samples (but not in whole hippocampus preparations). These results imply fast variations on the biophysics and molecular expression of Na currents of rat hippocampal CA1 neurones, throughout the feeding cycle. Thus, one may expect a differentiated regulation of the intrinsic neuronal excitability, which may account for the role of the hippocampus as a processor of satiety information.
海马体作为能量平衡的枢纽的功能是当前广泛关注的主题。本研究旨在通过研究进食周期对急性分离的 Wistar 大鼠海马 CA1 神经元电压门控钠 (Na ) 电流的影响，为这方面提供更多证据。具体而言，我们应用膜片钳技术（全细胞膜片钳和内面向外单通道）评估了进食和禁食条件对 Na 电流内在生物物理特性的影响。此外，还使用质谱和 Western 印迹实验来研究进食周期对大鼠海马体 Na 通道群体的影响。在取自进食和禁食动物的神经元中记录 Na 电流（分别称为“进食神经元”和“禁食神经元”）。与禁食神经元相比，进食神经元的全细胞 Na 电流显示出更大的平均最大电流密度和更高的“窗口电流”幅度。我们证明，这些结果得到了以下证据的支持：进食神经元中的单通道 Na 电导增加，以及进食样本的质膜富集部分（而不是整个海马体制剂）中的 Nav1.2 通道密度增加。这些结果表明，在整个进食周期中，大鼠海马 CA1 神经元的 Na 电流的生物物理学和分子表达发生了快速变化。因此，人们可能会期望内在神经元兴奋性的差异化调节，这可能解释了海马体作为饱腹感信息处理器的作用。
