Sík A, Hájos N, Gulácsi A, Mody I, Freund T F
Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony utca 43, Budapest, H-1083, Hungary.
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3245-50. doi: 10.1073/pnas.95.6.3245.
The Ca2+/calmodulin-dependent protein phosphatase 2B or calcineurin (CN) participates in several Ca2+-dependent signal transduction cascades and, thus, contributes to the short and long term regulation of neuronal excitability. By using a specific antibody to CN, we demonstrate its absence from hippocampal interneurons and illustrate a physiological consequence of such CN deficiency. Consistent with the lack of CN in interneurons as detected by immunocytochemistry, the CN inhibitors FK-506 or okadaic acid significantly prolonged N-methyl-D-aspartate channel openings recorded in the cell-attached mode in hippocampal principal cells but not those recorded in interneurons. Interneurons were also devoid of Ca2+/calmodulin-dependent protein kinase IIalpha, yet many of their nuclei contained the cyclic AMP-responsive element binding protein. On the basis of the CN and Ca2+/calmodulin-dependent protein kinase IIalpha deficiency of interneurons, entirely different biochemical mechanisms are expected to govern Ca2+-dependent neuronal plasticity in interneurons versus principal cells.
钙离子/钙调蛋白依赖性蛋白磷酸酶2B即钙调神经磷酸酶（CN）参与多种钙离子依赖性信号转导级联反应，因此有助于对神经元兴奋性进行短期和长期调节。通过使用针对CN的特异性抗体，我们证明其在海马中间神经元中不存在，并阐述了这种CN缺乏的生理后果。与免疫细胞化学检测到的中间神经元中缺乏CN一致，CN抑制剂FK-506或冈田酸显著延长了海马主细胞在细胞贴附模式下记录的N-甲基-D-天冬氨酸通道开放时间，但在中间神经元中记录的开放时间则未延长。中间神经元也缺乏钙离子/钙调蛋白依赖性蛋白激酶IIα，但其许多细胞核中含有环磷酸腺苷反应元件结合蛋白。基于中间神经元的CN和钙离子/钙调蛋白依赖性蛋白激酶IIα缺乏，预计中间神经元与主细胞中钙离子依赖性神经元可塑性的生化机制完全不同。
