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

Neuron. 2001 Sep 27;31(6):1015-25. doi: 10.1016/s0896-6273(01)00449-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Action Potentials / drug effects
  • Alkaloids / pharmacology
  • Animals
  • Calcium / metabolism*
  • Carbazoles*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / pharmacology
  • Cyclic GMP / physiology*
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Guanylate Cyclase / antagonists & inhibitors
  • Guanylate Cyclase / metabolism
  • Indoles*
  • Ion Channel Gating / drug effects
  • Ion Transport / drug effects
  • Ionomycin / pharmacology
  • Isoquinolines / pharmacology
  • Large-Conductance Calcium-Activated Potassium Channels
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / physiology
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type I
  • Nitroprusside / pharmacology
  • Oxadiazoles / pharmacology
  • Patch-Clamp Techniques
  • Photolysis
  • Pituitary Gland, Posterior / drug effects
  • Pituitary Gland, Posterior / physiology*
  • Potassium / metabolism*
  • Potassium Channels / drug effects
  • Potassium Channels / physiology*
  • Potassium Channels, Calcium-Activated*
  • Quinoxalines / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sodium / metabolism
  • Sodium Channels / metabolism
  • Sulfonamides*
  • Thionucleotides / pharmacology

Substances

  • 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
  • Alkaloids
  • Carbazoles
  • Enzyme Inhibitors
  • Indoles
  • Isoquinolines
  • Large-Conductance Calcium-Activated Potassium Channels
  • Nerve Tissue Proteins
  • Oxadiazoles
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Quinoxalines
  • Sodium Channels
  • Sulfonamides
  • Thionucleotides
  • KT 5823
  • Nitroprusside
  • Nitric Oxide
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-GMP
  • Ionomycin
  • N-(2-guanidinoethyl)-5-isoquinolinesulfonamide
  • Sodium
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Cyclic GMP-Dependent Protein Kinases
  • Guanylate Cyclase
  • Cyclic GMP
  • Potassium
  • Calcium
  • 1-Methyl-3-isobutylxanthine