Neuromedin U Depolarizes Rat Hypothalamic Paraventricular Nucleus Neurons In Vitro by Enhancing I H Channel Activity

The effect of neuromedin U (NMU) on rat paraventricular nucleus (PVN) neurons was examined using whole cell patch-clamp recordings. Under current-clamp, 31% of PVN parvocellular neurons (n = 243) were depolarized by 100 nM NMU, but magnocellular neurons were not affected. NMU (10 nM to 1 microM) resulted in increased basal firing rate and depolarization in a dose-dependent manner with an EC50 of 70 nM. NMU-induced depolarization was unaffected by co-perfusion with 0.5 microM TTX + 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) + 10 microM bicuculline. Extracellular application of 70 microM ZD 7288 completely inhibited NMU-induced depolarization. Under voltage-clamp, 1 microM NMU produced negligible inward current but did increase the hyperpolarization-activated current (IH) at step potentials less than -80 mV. The effects of NMU on IH were voltage-dependent, and NMU shifted the IH conductance-voltage relationship (V1/2) by about 10.8 mV and enhanced IH kinetics without changing the slope constant (k). Extracellular application of 70 microM ZD 7288 or 3 mM Cs+ blocked IH and the effects of NMU in voltage-clamp. These results suggest that NMU selectively depolarizes the subpopulation of PVN parvocellular neurons via enhancement of the hyperpolarization-activated inward current.