CGMP-mediated facilitation in nerve terminals by enhancement of the spike afterhyperpolarization

cGMP has long been suspected to play a role in synaptic plasticity, but the inaccessibility of nerve terminals to electrical recording has impeded tes ts of this hypothesis. In posterior pituitary nerve terminals, nitric oxide enhanced Ca2+-activated K+ channel activity by activating guanylate cyclas e and PKG. This enhancement occured only at depolarized potentials, so the spike threshold remained unaltered but the afterhyperpolarization became la rger. During spike trains, the enhanced afterhyperpolarization promoted Na channel recovery from inactivation, thus reducing action potential failure s and allowing more Ca2+ to enter. Activating guanylate cyclase, either wit h applied nitric oxide, or with physiological stimulation to activate nitri c oxide synthase, increased action potential firing. Thus, the cGMP/nitric oxide cascade generates a shortterm, use-dependent enhancement of release.