Klyachko V A, Ahern G P, Jackson M B
Department of Physiology and Biophysics, PhD Program, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706, USA.
Neuron. 2001 Sep 27;31(6):1015-25. doi: 10.1016/s0896-6273(01)00449-4.
cGMP has long been suspected to play a role in synaptic plasticity, but the inaccessibility of nerve terminals to electrical recording has impeded tests of this hypothesis. In posterior pituitary nerve terminals, nitric oxide enhanced Ca(2+)-activated K+ channel activity by activating guanylate cyclase and PKG. This enhancement occurred only at depolarized potentials, so the spike threshold remained unaltered but the afterhyperpolarization became larger. During spike trains, the enhanced afterhyperpolarization promoted Na+ channel recovery from inactivation, thus reducing action potential failures and allowing more Ca(2+) to enter. Activating guanylate cyclase, either with applied nitric oxide, or with physiological stimulation to activate nitric oxide synthase, increased action potential firing. Thus, the cGMP/nitric oxide cascade generates a short-term, use-dependent enhancement of release.
长期以来，人们一直怀疑环磷酸鸟苷（cGMP）在突触可塑性中发挥作用，但神经末梢难以进行电记录阻碍了对这一假设的验证。在垂体后叶神经末梢中，一氧化氮通过激活鸟苷酸环化酶和蛋白激酶G增强钙激活钾通道活性。这种增强仅在去极化电位时出现，因此动作电位阈值保持不变，但超极化后电位变大。在一串动作电位期间，增强的超极化后电位促进钠通道从失活状态恢复，从而减少动作电位失败并允许更多的钙离子进入。应用一氧化氮或通过生理刺激激活一氧化氮合酶来激活鸟苷酸环化酶，均可增加动作电位发放。因此，cGMP/一氧化氮级联反应产生了一种短期的、与使用相关的释放增强。
