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 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.
Klyachko
V A
VA
Department of Physiology and Biophysics, PhD Program, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706, USA.
Ahern
G P
GP
Jackson
M B
MB
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007211:Indoles; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010782:Photolysis; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D013449:Sulfonamides; D013873:Thionucleotides / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009419:Nerve Tissue Proteins; D010069:Oxadiazoles; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011810:Quinoxalines; D015222:Sodium Channels; D013449:Sulfonamides; D013873:Thionucleotides; C073601:KT 5823; D009599:Nitroprusside; D009569:Nitric Oxide; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D015759:Ionomycin; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D012964:Sodium; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine