Lev-Ram V, Makings L R, Keitz P F, Kao J P, Tsien R Y
Department of Pharmacology, University of California, San Diego, La Jolla 92093-0647, USA.
Neuron. 1995 Aug;15(2):407-15. doi: 10.1016/0896-6273(95)90044-6.
The role of nitric oxide (NO) in the induction of long-term depression (LTD) in the cerebellum was explored using a new, organic, membrane-impermeant form of caged NO. NO photolytically released inside Purkinje neurons mimicked parallel fiber (PF) activity in synergizing with brief postsynaptic depolarization to induce LTD. Such LTD required a delay of < 50 ms between the end of photolysis and the onset of depolarization, was prevented by intracellular Ca2+ chelation, and was mutually occlusive with LTD conventionally produced by PF activation plus depolarization. Bath application of NO synthase inhibitor or of myoglobin, a NO trap, prevent LTD induction via PF stimulation, but not that from intracellular uncaged NO, whereas intracellular myoglobin blocked both protocols. NO is therefore an anterograde transmitter in LTD induction. A biochemical requirement for simultaneous NO and elevation of intracellular free Ca2+ would explain why PF activity must coincide with postsynaptic action potentials.
使用一种新型的、有机的、不能透过细胞膜的笼形一氧化氮（NO），探讨了一氧化氮（NO）在小脑长时程抑制（LTD）诱导中的作用。在浦肯野神经元内光解释放的NO与短暂的突触后去极化协同作用，模拟平行纤维（PF）活动以诱导LTD。这种LTD在光解结束和去极化开始之间需要<50毫秒的延迟，可被细胞内Ca2+螯合所阻止，并且与由PF激活加去极化常规产生的LTD相互闭塞。浴应用NO合酶抑制剂或肌红蛋白（一种NO捕获剂）可阻止通过PF刺激诱导的LTD，但不能阻止细胞内未笼化NO诱导的LTD，而细胞内肌红蛋白则阻断了这两种方案。因此，NO是LTD诱导中的一种顺行递质。同时需要NO和细胞内游离Ca2+升高的生化要求可以解释为什么PF活动必须与突触后动作电位同时发生。
