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The Journal of Neuroscience, September 15, 2001, 21(18):7143-7152
Neuronal P2X7 Receptors Are Targeted to Presynaptic
Terminals in the Central and Peripheral Nervous Systems
Susan A.
Deuchars1,
Lucy
Atkinson1,
Ruth E.
Brooke1,
Hanny
Musa1,
Carol J.
Milligan1,
Trevor F. C.
Batten3,
Noel J.
Buckley2,
Simon H.
Parson1, and
Jim
Deuchars1
1 School of Biomedical Sciences, University of Leeds,
LS2 9NQ, Leeds, United Kingdom, Schools of
2 Biochemistry and Molecular Biology, and
3 Medicine, University of Leeds, LS2 9JT, Leeds, United
Kingdom
The ionotropic ATP receptor subunits P2X1-6 receptors
play important roles in synaptic transmission, yet the P2X7
receptor has been reported as absent from neurons in the normal adult
brain. Here we use RT-PCR to demonstrate that transcripts for the
P2X7 receptor are present in extracts from the medulla
oblongata, spinal cord, and nodose ganglion. Using in
situ hybridization mRNA encoding, the P2X7 receptor
was detected in numerous neurons throughout the medulla oblongata and
spinal cord. Localizing the P2X7 receptor protein with
immunohistochemistry and electron microscopy revealed that it is
targeted to presynaptic terminals in the CNS. Anterograde labeling of
vagal afferent terminals before immunohistochemistry confirmed the
presence of the receptor in excitatory terminals. Pharmacological
activation of the receptor in spinal cord slices by addition of 2'- and
3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP; 30 µM) resulted in glutamate mediated excitation of recorded neurons, blocked by P2X7 receptor antagonists oxidized ATP
(100 µM) and Brilliant Blue G (2 µM). At
the neuromuscular junction (NMJ) immunohistochemistry revealed that the
P2X7 receptor was present in motor nerve terminals.
Furthermore, motor nerve terminals loaded with the vital dye FM1-43 in
isolated NMJ preparations destained after application of BzATP (30 µM). This BzATP evoked destaining is blocked by oxidized
ATP (100 µM) and Brilliant Blue G (1 µM).
This indicates that activation of the P2X7 receptor promotes release of vesicular contents from presynaptic terminals. Such
a widespread distribution and functional role suggests that the
receptor may be involved in the fundamental regulation of synaptic
transmission at the presynaptic site.
Key words:
ATP; purine receptor; synaptic transmission; excitatory
amino acid transmission; spinal cord; medulla oblongata; neuromuscular
junction
Copyright © 2001 Society for Neuroscience 0270-6474/01/21187143-10$05.00/0
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