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The Journal of Neuroscience, June 15, 2002, 22(12):4767-4775
ATP as a Putative Sensory Mediator: Activation of Intrinsic
Sensory Neurons of the Myenteric Plexus via P2X Receptors
Paul P.
Bertrand and
Joel C.
Bornstein
Department of Physiology, University of Melbourne, Parkville,
Victoria 3010, Australia
The mucosal terminals of sensory neurons intrinsic to the wall of
the intestine are sensitive to the chemical environment within the
lumen. Lumenal stimuli probably release sensory mediators from the
mucosal epithelium, which then activate the nerve terminals indirectly.
Here, we tested the idea that ATP activates intrinsic sensory
nerve terminals in a way consistent with its being a sensory mediator.
We made intracellular recordings from intrinsic sensory neurons located
in the myenteric plexus [identified as AH neurons, which are neurons
with a long-lasting afterhyperpolarization following the action
potential (AP)], located within 1 mm of intact mucosa. Focal
electrical stimulation of the mucosa was used to locate and map regions
innervated by each neuron. Application of ATP (1-2 mM in
the pressure pipette) to these regions elicited trains of APs that
originated at the sensory terminals. ATP- -S produced a similar
response, but  , -methylene ATP and 2-methylthio-ATP were only
weakly active. The P2 receptor antagonist
pyridoxalphosphate-6-azophenyl-2',5'-disulphonic acid (PPADS) (60 µM in the bath) abolished the APs evoked by ATP and
ATP--S but spared similar responses evoked by 5-hydroxytryptamine (5-HT). Another P2 receptor antagonist suramin (100 µM in
the bath) did not significantly change the number of APs evoked by ATP.
Either ATP or ,-methylene ATP desensitized the ATP-evoked APs;
50% recovery occurred after ~5 sec. The number of APs evoked by ATP
was reduced, but not abolished, by the selective 5-HT3 receptor antagonist granisetron (1 µM in the bath).
ATP was applied to the cell bodies of sensory neurons to investigate
whether the cell bodies express the same P2X receptor as the terminals.
ATP evoked a fast depolarization associated with a reduction in input
resistance and a reversal potential of  11 mV. This depolarization was
potentiated by suramin and blocked by PPADS.
We conclude that activation of an atypical excitatory P2X
receptor by ATP triggers AP generation in the mucosal processes of the
sensory neurons; endogenous 5-HT release may also contribute to
activation of the nerve terminals. A similar P2X receptor exists on the
cell body of the sensory neuron. Together, these data are consistent
with a role for ATP as a sensory mediator in gastrointestinal chemosensory transduction.
Key words:
ATP; electrophysiology; intestine; sensory neuron; sensory transduction; serotonin
Copyright © 2002 Society for Neuroscience 0270-6474/02/22124767-09$05.00/0
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