Interleukin-1beta depolarizes magnocellular neurons in the paraventricular nucleus of the hypothalamus through prostaglandin-mediated activation of a non selective cationic conductance.
Interleukin-1beta (IL-1beta) is involved in hypothalamic regulation of the neuroimmune response by influencing the synthesis and secretion of corticotropin releasing hormone (CRH), vasopressin (VP) and other stress-related mediators. VP secretion from magnocellular (MNC) neurons of the paraventricular nucleus (PVN) of the hypothalamus at the posterior pituitary and/or median eminence contributes to increasing adrenocorticotropin hormone (ACTH) output and ultimately glucocorticoid release, which then contributes to the stress response. In this study, using whole-cell patch clamp recordings from neurons in a slice preparation of the rat PVN, we show that MNC neurons are also influenced by IL-1beta. In response to 1 nM IL-1beta, 62% of MNC neurons tested depolarized (mean depolarization=10.9+/-1.4 mV); effects which were maintained in the presence of a sodium channel blocker, tetrodotoxin (TTX). The effects of IL-1beta on MNC neurons were blocked in the presence of a specific cyclooxygenase (COX)-2 inhibitor, NS-398, indicating a dependence on prostaglandins (PG) in mediating these effects. In response to direct application of 1 muM PGE2, 57% of MNC neurons depolarized, exhibiting a membrane potential change similar to that induced by IL-1beta (mean depolarization=7.8+/-1.1 mV). Voltage clamp experiments examining the effects of PGE2 on the currents evoked by slow voltage ramps revealed activation of a conductance characteristic of a non-selective cationic conductance (NSCC) (voltage-independent, with a reversal potential of -41.8+/-7.6 mV), suggesting that this prostanoid directly modifies cationic currents in MNC neurons. These data provide evidence that IL-1beta depolarizes MNC neurons in the PVN as a result of prostaglandin-mediated activation of a NSCC.
Ferri
Catharine C
CC
Department of Physiology, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
Yuill
Erik A
EA
Ferguson
Alastair V
AV
D000818:Animals; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D007375:Interleukin-1; D011453:Prostaglandins