Feeding cycle alters the biophysics and molecular expression of voltage-gated Na⁺ currents in rat hippocampal CA1 neurones

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.