Interplay among cGMP, cAMP, and Ca2+ in Living Olfactory Sensory Neurons In Vitro and In Vivo
0301 basic medicine
0303 health sciences
Ca2+; neurons; Fluorescence; Calcium signalling; cAMP
Cell Count
Immunohistochemistry
Olfactory Receptor Neurons
Rats
03 medical and health sciences
olfactory sensory neurons
Cyclic AMP
Animals
Calcium
Phosphorylation
real time imaging
cGMP Ca2+ cAMP
Cyclic AMP Response Element-Binding Protein
Cyclic GMP
Cells, Cultured
Signal Transduction
DOI:
10.1523/jneurosci.6722-10.2011
Publication Date:
2011-06-08T19:22:46Z
AUTHORS (6)
ABSTRACT
The mechanism of cGMP production in olfactory sensory neurons (OSNs) is poorly understood, although this messenger takes part in several key processes such as adaptation, neuronal development, and long-term cellular responses to odorant stimulation. Many aspects of the regulation of cGMP in OSNs are still unknown or highly controversial, such as its subcellular heterogeneity, mechanism of coupling to odorant receptors and downstream targets. Here, we have investigated the dynamics and the intracellular distribution of cGMP in living rat OSNs in culture transfected with a genetically encoded sensor for cGMP. We demonstrate that OSNs treated with pharmacological stimuli able to activate membrane or soluble guanylyl cyclase (sGC) presented an increase in cGMP in the entire neuron, from cilia-dendrite to the axon terminus-growth cone. Upon odorant stimulation, a rise in cGMP was again found in the entire neuron, including the axon terminus, where it is locally synthesized. The odorant-dependent rise in cGMP is due to sGC activation by nitric oxide (NO) and requires an increase of cAMP. The link between cAMP and NO synthase appears to be the rise in cytosolic Ca(2+) concentration elicited by either plasma membrane Ca(2+) channel activation or Ca(2+) mobilization from stores via the guanine nucleotide exchange factor Epac. Finally, we show that a cGMP rise can elicit both in vitro and in vivo the phosphorylation of nuclear CREB, suggesting that this signaling pathway may be relevant for both local events (pathfinding, neurotransmitter release) and more distal processes involving gene expression regulation.
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