Prolonged presynaptic posttetanic cyclic GMP signaling in Drosophila motoneurons

By Dinara Shakiryanova and Edwin S. Levitan
PNAS 105 (36): 13611-13613

1) The activity of cyclic nucleotide activity is first shown at the terminal. It is cGMP, not cAMP.
2) NO generation and activation both occur in the presynaptic terminal
3) It is surprisingly long lasting.


FRET-based cAMP imaging showed a Ca-dependent sustained increase of cAMP (or cyclic nucleotide) after a brief activation of synapse (fly neuromuscular synapse).

However,
1) Ca-dependent increase of cyclic nucleotide (cAMP). Both extracellular and RyR-mediated.
But,
- Ca-stimulated AC mutant has no effect.
- cAMP-specific PDE mutant has no effect.

2) This is cGMP instead of cAMP?
- GC inhibitor (ODQ) reduced the FRET signal.
- NOS inhibitor and NO scavenger reduced it too.
- Expression of cGMP-specific PDE shortened the signal.
- IBMX indeed extend the cGMP signal duration.

NOS-guanylyl cyclase-mediated presynaptic cGMP synthesis.

ODQ: guanylyl cyclase inhibitor
L-NAME: NOS inhibitor
PTIO: NO scavenger

They don’t show the effect on synaptic strength…