Laabich A, Cooper N G
Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, KY, 40202, USA.
Exp Eye Res. 1999 Jun;68(6):703-13. doi: 10.1006/exer.1999.0664.
This study is concerned with the transmitter-mediated regulation of the alpha(50 kDa) and beta(60 kDa) subunits of calcium calmodulin dependent protein kinase II (CamKII) in the adult rat retina. The level of antibody binding to the CamKII and the activity of CamKII were found to be increased after intravitreal injection of glutamate. Changes in the levels of the antibody-binding to the subunits of CamKII were observed in different subcellular fractions of the retina with a maximum response observed in crude synaptic membrane fractions. The glutamate mediated increases in CamKII were specific and blocked by 3,5-Dimethyl-1 adamantanamine; 3,5-Dimethylamantadine (Memantine), (+/-) 2-Amino-5-Phosphopentonic (AP-5) and 6-Cyano-7-Nitroquinoxaline-2,3-Dione (CNQX) but not with dl -2-Amino-3-Phosphono-Propionic (AP-3). The results indicate that the retinal neurotransmitter, glutamate, can regulate retinal CamKII activity through ionotropic but not metabotropic glutamate receptors. NMDA-receptors were found to be necessary but insufficient to stimulate CamKII. A model in which cooperative interaction between NMDA and non-NMDA glutamate receptors/ion channels is presented to explain the glutamate stimulated increases in CamKII activity in the retina.
本研究关注成年大鼠视网膜中钙调蛋白依赖性蛋白激酶II（CamKII）的α（50 kDa）和β（60 kDa）亚基的递质介导调节。玻璃体内注射谷氨酸后，发现与CamKII的抗体结合水平和CamKII的活性增加。在视网膜的不同亚细胞组分中观察到与CamKII亚基的抗体结合水平的变化，在粗制突触膜组分中观察到最大反应。谷氨酸介导的CamKII增加是特异性的，并被3,5 - 二甲基 - 1 - 金刚烷胺；3,5 - 二甲基金刚烷胺（美金刚）、（±）2 - 氨基 - 5 - 磷酸戊酸（AP - 5）和6 - 氰基 - 7 - 硝基喹喔啉 - 2,3 - 二酮（CNQX）阻断，但不被dl - 2 - 氨基 - 3 - 膦酰丙酸（AP - 3）阻断。结果表明，视网膜神经递质谷氨酸可通过离子型而非代谢型谷氨酸受体调节视网膜CamKII活性。发现NMDA受体对于刺激CamKII是必要的，但并不充分。提出了一种模型，其中NMDA和非NMDA谷氨酸受体/离子通道之间的协同相互作用可解释谷氨酸刺激的视网膜中CamKII活性增加。
