Interleukin 1β Directly Excites Isolated Rat Supraoptic Neurons via Upregulation of the Osmosensory Cation Current

Previous studies have shown that interleukin-1β (IL-1β) can excite the magnocellular neurosecretory cells (MNCs) of the hypothalamus. However it is not known if IL-1β can have direct IL-1 receptor type 1 (IL-1R1)-mediated effects on MNCs, and little is known about the cellular mechanisms by which IL-1β influences electrical activity in these cells. Here we used patch-clamp recordings to examine the effects of IL1β on acutely isolated rat MNCs. We found that IL-1β directly excites MNCs in a dosedependent manner and that this response can be blocked by an inhibitor of the IL-1R1. Voltage clamp analysis of the current evoked by IL-1β revealed a linear current-voltage relationship between -90 and -20 mV, and a reversal potential near -35 mV. This value was not affected by reducing the concentration of chloride ions in the external solution, indicating the involvement of a non-selective cation conductance. The effects of IL-1β were inhibited by Na-salicylate, an inhibitor of cyclooxygenase. Moreover the effects of IL-1β were mimicked and occluded by prostaglandin E2 (PGE2 ), and were inhibited by AH-23848, an antagonist of the EP4 receptor. The current evoked by IL-1β was also abolished by 100 μM Gd, but was significantly larger when examined in cells preshrunk by negative pressure applied via the recording pipette. IL-1β alone did not cause changes in cell volume, or in the mechanosensitivity of MNCs. We conclude that IL-1β directly excites MNCs via an IL-1R1-mediated induction of PGE2 synthesis and EP4 receptor-dependent autocrine upregulation of the nonselective cation conductance that underlies osmoreception.