title: IL-1beta directly excites isolated rat supraoptic neurons via upregulation of the osmosensory cation current.
abstract: Previous studies have shown that IL-1beta can excite the magnocellular neurosecretory cells (MNCs) of the hypothalamus. However, it is not known whether IL-1beta 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-1beta influences electrical activity in these cells. Here, we used patch-clamp recordings to examine the effects of IL-1beta on acutely isolated rat MNCs. We found that IL-1beta directly excites MNCs in a dose-dependent manner and that this response can be blocked by an inhibitor of the IL-1R1. Voltage-clamp analysis of the current evoked by IL-1beta 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 nonselective cation conductance. The effects of IL-1beta were inhibited by Na-salicylate, an inhibitor of cyclooxygenase. Moreover, the effects of IL-1beta were mimicked and occluded by PGE2, and were inhibited by AH-23848, an antagonist of the PGE2 type 4 (i.e., EP4) receptor. The current evoked by IL-1beta was also abolished by 100 microM gadolinium (Gd3+), but was significantly larger when examined in cells preshrunk by negative pressure applied via the recording pipette. IL-1beta alone did not cause changes in cell volume nor in the mechanosensitivity of MNCs. We conclude that IL-1beta 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.
authors.affiliation: Centre for Research in Neuroscience, Montreal General Hospital and McGill University, Montreal, QC, Canada.
authors.forename: Yassar
authors.initials: Y
authors.lastname: Chakfe
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Charles W
authors.initials: CW
authors.lastname: Bourque
mesh_terms: D000818:Animals; D002469:Cell Separation; D048429:Cell Size / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology; D019899:Paracrine Communication / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D007473:Ion Channels; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases