Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB219

Poster Communications

Impact of feeding cycle upon the biophysics of sodium and calcium currents of rat hippocampal CA1 neurones.

A. E. Bastos1, P. Lima1

1. Physiology, Nova Medical School, Lisbon, Lisbon, Portugal.

Feeding behaviour is regulated by the central nervous system, through a concerted endeavour of different brain areas. The hippocampus, historically regarded as a substrate for learning and memory processes, has also been implicated in such energy regulation (1, 2). In recent years, researchers have established that hippocampal neurones form a memory of a meal and act to delay meal initiation during the postprandial period (3, 4). By assessing the impact of feeding cycle upon the sodium and calcium currents of Wistar rat hippocampal CA1 neurones, the present study identifies possible neuronal mechanisms by which hippocampus processes satiety and meal termination. Two classes of neurones were used: those obtained from animals that fasted overnight (‘fasted neurones') and those from animals that, after such period, were fed (‘fed neurones'). Voltage-gated Na+ currents were recorded using whole-cell (WC) and excised inside-out configurations. Fed neurones, in comparison to fasted neurones, showed increased mean maximum macroscopic Na+ current density (1.5 ±, n=18 vs. 1±, n=28) and a greater mean single-channel conductance (16.7 ± 0.76pS, n=8 vs. 12.6 ± 1.30pS, n=8). Furthermore, the larger amplitude of the ‘window current' obtained in fed neurones, derived from hyperpolarized activation curves and depolarized steady-state of inactivation curves (h∞), indicates a greater Na+ channel availability to respond to activation. Such variation is supported by the western blotting results that indicate a higher concentration of Nav1.2 isoform at the plasma membrane-enriched fractions of hippocampus of fed animals. Voltage-gated Ca2+ currents were analysed with WC recordings. It was observed heterogeneity in Ca2+ currents, here sorted into three categories - ‘A', ‘B', and ‘C' currents. The differential distribution of these currents between fed and fasted neurones determined significant alterations on the inactivation properties of Ca2+ currents. The increased values of the time-constant of inactivation, observed upon feeding, can be ascribed to a conspicuous slowly-inactivating current mainly assigned to fed neurones (current ‘A'), as oppose to the fastest kinetics of inactivation, solely seen in fasted neurones (current ‘C'). Overall, the results indicate a) a variation in the biophysics and expression of voltage gated Na+ channels and b) a facilitated entry of Ca2+ into the soma of fed neurones. Altogether, these observations suggest impact of feeding on neuronal excitability and Ca2+-dependent intracellular events, which may lead to a subsequent increase of neuronal synaptic performance. Hence, a positive relationship between feeding and higher levels of synaptic plasticity-related phenomena (formation and consolidation of memories) is suggested, which could help to explain the role of hippocampus on the regulation of energy intake, mainly due to its role on meal-related episodic memories.

Where applicable, experiments conform with Society ethical requirements