Bading H, Ginty D D, Greenberg M E
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Science. 1993 Apr 9;260(5105):181-6. doi: 10.1126/science.8097060.
Calcium ions (Ca2+) act as an intracellular second messenger and can enter neurons through various ion channels. Influx of Ca2+ through distinct types of Ca2+ channels may differentially activate biochemical processes. N-Methyl-D-aspartate (NMDA) receptors and L-type Ca2+ channels, two major sites of Ca2+ entry into hippocampal neurons, were found to transmit signals to the nucleus and regulated gene transcription through two distinct Ca2+ signaling pathways. Activation of the multifunctional Ca(2+)-calmodulin-dependent protein kinase (CaM kinase) was evoked by stimulation of either NMDA receptors or L-type Ca2+ channels; however, activation of CaM kinase appeared to be critical only for propagating the L-type Ca2+ channel signal to the nucleus. Also, the NMDA receptor and L-type Ca2+ channel pathways activated transcription by means of different cis-acting regulatory elements in the c-fos promoter. These results indicate that Ca2+, depending on its mode of entry into neurons, can activate two distinct signaling pathways. Differential signal processing may provide a mechanism by which Ca2+ controls diverse cellular functions.
钙离子（Ca2+）作为细胞内第二信使，可通过多种离子通道进入神经元。通过不同类型的Ca2+通道流入的Ca2+可能会以不同方式激活生化过程。N-甲基-D-天冬氨酸（NMDA）受体和L型Ca2+通道是Ca2+进入海马神经元的两个主要位点，研究发现它们通过两条不同的Ca2+信号通路将信号传递至细胞核并调节基因转录。NMDA受体或L型Ca2+通道的刺激均可诱发多功能Ca(2+)-钙调蛋白依赖性蛋白激酶（CaM激酶）的激活；然而，CaM激酶的激活似乎仅对将L型Ca2+通道信号传递至细胞核至关重要。此外，NMDA受体和L型Ca2+通道途径通过c-fos启动子中不同的顺式作用调节元件激活转录。这些结果表明，Ca2+根据其进入神经元的方式，可激活两条不同的信号通路。差异信号处理可能提供了一种Ca2+控制多种细胞功能的机制。
