Modulation of glutamate-induced outward current by prostaglandin E 2 in rat dissociated preoptic neurons

Abstract

The preoptic/anterior hypothalamus (POA) is one of the major brain regions where cytokines and their related mediators (i.e., prostaglandins) exert diverse actions. In the present study, the modulatory effects of prostaglandin E 2 (PGE 2) on the glutamate-induced membrane currents were examined using perforated-patch clamp method in rat POA neurons that had been mechanically dissociated by vibration without enzyme treatment. Application of glutamate through U-tube induced a slow outward current following fast inward ionotroic current at a holding membrane potential of −30 mV. The slow outward current was also induced by N-methyl- d-aspartate (NMDA), accompanied by an increased membrane conductance, and inhibited by perfusion with Ca 2+-free solution, tetraethylammonium chloride (TEA), and apamin, suggesting a Ca 2+-dependent K + current (KCa) activated by Ca 2+ entry through NMDA channels. Perfusion with PGE 2 at 0.1–10 μM, a principal mediator of fever and neuroendocrine control at the POA, did not produce apparent current by itself, but selectively potentiated the glutamate- or NMDA-induced KCa without affecting inward currents. The KCa induced by activation of NMDA receptors may serve as a feedback mechanism and the modulatory effects of PGE 2 on the KCa may have an important physiological significance.