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

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 microM, 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.