Cyclic ADP-ribose and calcium-induced calcium release regulate neurotransmitter release at a cholinergic synapse of Aplysia

J Physiol. 1998 Mar 1;507 ( Pt 2)(Pt 2):405-14. doi: 10.1111/j.1469-7793.1998.405bt.x.


1. Presynaptic injection of cyclic ADP-ribose (cADPR), a modulator of the ryanodine receptor, increased the postsynaptic response evoked by a presynaptic spike at an identified cholinergic synapse in the buccal ganglion of Aplysia californica. 2. The statistical analysis of long duration postsynaptic responses evoked by square depolarizations of the voltage-clamped presynaptic neurone showed that the number of evoked acetylcholine (ACh) quanta released was increased following cADPR injection. 3. Overloading the presynaptic neurone with cADPR led to a transient increase of ACh release followed by a depression. 4. cADPR injections did not modify the presynaptic Ca2+ current triggering ACh release. 5. Ca2+ imaging with the fluorescent dye rhod-2 showed that cADPR injection rapidly increased the free intracellular Ca2+ concentration indicating that the effects of cADPR on ACh release might be related to Ca2+ release from intracellular stores. 6. Ryanodine and 8-amino-cADPR, a specific antagonist of cADPR, decreased ACh release. 7. ADP-ribosyl cyclase, which cyclizes NAD+ into cADPR, was present in the presynaptic neurone as shown by reverse transcriptase-polymerase chain reaction experiments. 8. Application of NAD+, the substrate of ADP-ribosyl cyclase, increased ACh release and this effect was prevented by both ryanodine and 8-amino-cADPR. 9. These results support the view that Ca(2+)-induced Ca2+ release might be involved in the build-up of the Ca2+ concentration which triggers ACh release, and thus that cADPR might have a role in transmitter release modulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Adenosine Diphosphate Ribose / analogs & derivatives*
  • Adenosine Diphosphate Ribose / pharmacology
  • Animals
  • Aplysia / metabolism*
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium / physiology*
  • Cyclic ADP-Ribose
  • Electrophysiology
  • Fluorescent Dyes
  • Ganglia, Invertebrate / drug effects
  • Ganglia, Invertebrate / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • NAD / metabolism
  • NAD / pharmacology
  • Neurotransmitter Agents / metabolism*
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / metabolism*
  • Patch-Clamp Techniques
  • Polymerase Chain Reaction
  • Receptors, Presynaptic / drug effects
  • Ryanodine Receptor Calcium Release Channel / drug effects
  • Synapses / drug effects
  • Synapses / metabolism*


  • Fluorescent Dyes
  • Neurotransmitter Agents
  • Receptors, Presynaptic
  • Ryanodine Receptor Calcium Release Channel
  • NAD
  • Cyclic ADP-Ribose
  • Adenosine Diphosphate Ribose
  • Acetylcholine
  • Calcium