Urotensin Ⅱ inhibits electrical activity of hippocampal CA1 neurons by potentiating the GABAA recept

Objective To examine the effects of urotensin Ⅱ (UII) on the discharges of neurons in CA1 area of hippocampal slices by using extracellular recording technique. Results① In response to the application of UII (0.3, 3.0,30.0, 300.0 nmol/L, n =77) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 63/77 (81.8％) neurons were significantly decreased in a dose-dependent manner. ②Pretreatment with bicuculline( BIC, 100 μmol/L) , a specific GABAA receptor antagonist, led to a marked increase in the SDR of 6/7 (85.71％ ) neurons in an epileptiform pattern. The increased discharges were not significantly changed after UII (30.0 nmol/L) was applied into the perfusate for 2 min. ③ Pretreatment with picrotoxin (PIC, 50 μmol/L) , a selective blocker of Cl- channel, led to an increase in the SDR of all 8/8 (100％) neurons. The increased discharges were not influenced by the UII (30.0 nmol/L) applied.④Application of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L) into the perfusate for 2 min also significantly augmented the SDR of 14/16 (87.5％) neurons , then UII (30.0 nmol/L) applied into the perfusate reduced the increased the SDR of all 14/14 ( 100％ ) neurons. Conclusion These results suggest that UII may decrease neuronal activity by potentiating GABAA receptor-mediated Cl- current in hippocampal CA1 neurons, and involved with the mediation of nitric oxide.