Effects of agmatine on neuronal discharges in rat hippocampal CA1 area / 生理学报

ABSTRACT

The effects of agmatine (Agm) on the discharges of neurons in CA1 area of hippocampal slices were examined by using extracellular recording technique. The results are as follows. (1) In response to the application of Agm (0.1-1.0 micromol/L) into the superfusate for 2 min, the spontaneous discharge rates (SDR) of 38/47 (80.9%) neurons were decreased significantly in a dose-dependent manner, while that of 9/47 (19.1%) neurons showed no change in discharge rate; (2) pretreatment with L-glutamate (L-Glu, 0.2 mmol/L) led to a marked increase in SDR of 9/12 (75%) neurons in an epileptiform pattern and that of 2/12 (25%) neurons were not affected, then after Agm (1.0 micromol/L) was applied into the superfusate for 2 min, the epileptiform discharges were suppressed significantly; (3) in 7 neurons, perfusion of the selective L-type calcium channel agonist, Bay K-8644 (0.1 micromol/L), induced an increase in the SDR of 6/7 (85.7%) neurons, while that of 1/7 (14.3%) neuron showed no change, and the discharges were also decreased by application of Agm (1.0 micromol/L) into the superfusate; and (4) application of NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 micromol/L) into the superfusate 5 min later also significantly increased the SDR in all 13 (100%) neurons; then Agm (1.0 micromol/L) applied into the superfusate inhibited the discharges of 11/13 (84.6%) neurons, while those of 2/13 (15.4%) neurons were not affected. These results suggest that agmatine can inhibit the spontaneous discharges and L-glutamate-, Bay K-8644- and L-NAME-induced discharges of hippocampal CA1 neurons. These inhibitory effects of agmatine may be related to the blockade of NMDA receptors and a reduction in calcium influx in hippocampal neurons