Enhancement of synaptic transmission by cyclic AMP modulation of presynaptic Ih channels

Nat Neurosci. 2000 Feb;3(2):133-41. doi: 10.1038/72072.

Abstract

Presynaptic activation of adenylyl cyclase and subsequent generation of cAMP represent an important mechanism in the modulation of synaptic transmission. In many cases, short- to medium-term modulation of synaptic strength by cAMP is due to activation of protein kinase A and subsequent covalent modification of presynaptic ion channels or synaptic proteins. Here we show that presynaptic cAMP generation via serotonin receptor activation directly modulated hyperpolarization-activated cation channels (Ih channels) in axons. This modulation of Ih produced an increase in synaptic strength that could not be explained solely by depolarization of the presynaptic membrane. These studies identify a mechanism by which cAMP and Ih regulate synaptic plasticity.

Publication types

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

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Astacoidea
  • Axons / drug effects
  • Axons / enzymology
  • Axons / physiology
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic Nucleotide-Gated Cation Channels
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • In Vitro Techniques
  • Ion Channels / drug effects
  • Ion Channels / metabolism*
  • Muscles / cytology
  • Muscles / physiology
  • Neuromuscular Junction / metabolism
  • Phosphodiesterase Inhibitors / pharmacology
  • Potassium Channels
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / enzymology*
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines / pharmacology
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Theophylline / analogs & derivatives
  • Theophylline / pharmacology

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • Enzyme Inhibitors
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Phosphodiesterase Inhibitors
  • Potassium Channels
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines
  • ICI D2788
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Serotonin
  • 8-(4-sulfophenyl)theophylline
  • Theophylline
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases