摘要
应用细胞外记录单位放电技术,在大鼠海马脑片上观察了胍丁胺(agmatine,Agm)对CA1区神经元放电的影响。实验结果如下:(1)在47个海马脑片放电单位上灌流Agm(0.1-1.0μmoL/L)2 rain,有38个单位(80.9％)自发放电频率明显降低,且呈剂量依赖性,9个单位(19.1％)无明显的反应;(2)预先用0.2 mmol/L的L-谷氨酸(三-glutamate,L-Glu)灌流12个海马脑片放电单位,有9个单位(75％)放电频率明显增加,表现为癫痫样放电,在此基础上灌流Agm(1.0μmol/L)2 min,其癫痫样放电被抑制;(3)在7个海马脑片放电单位上给予L型钙通道激动剂:Bay K8644(0.1μmoL/L)时,有6个单位(85.7％)放电频率明显增加,另外1个单位(14.3％)无明显变化,再给予Agm(1.0μmol/L)2 min,其放电频率被明显抑制;(4)13个CA1放电单位,灌流50μmol/L-氧化氮合酶(NOS)抑制剂旷NG-nitro-L-arginine methyl ester(L-NAME)5 min后其放电频率明显增加,在此基础上再给予Agm(1.0 μmoL/L)2 min,有11个单位(84.6％)的放电频率被抑制,有2个单位(15.4％)的变化不明显。上述结果提示:胍丁胺能抑制海马CA1区神经元自发放电以及由谷氨酸、Bay K8644和L-NAME诱发的放电,这一抑制效应可能与胍丁胺阻断CA1区锥体细胞上的NMDA受体,并减少钙离子内流有关。
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 μmol/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 μmol/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 μmol/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. 0μmol/L) into the superfusate; and (4) application of NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L) into the superfusate 5 min later also significantly increased the SDR in all 13 (100% ) neurons; then Agm (1.0 μmol/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 agma- tine may be related to the blockade of NMDA receptors and a reduction in calcium influx in hippocampal neurons
出处
《生理学报》
CAS
CSCD
北大核心
2003年第6期717-721,共5页
Acta Physiologica Sinica
