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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 P2X_1-6 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

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21187143-10$05.00/0

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