Neuronal P2X7 receptors are targeted to presynaptic terminals in the central and peripheral nervous systems

Susan A. Deuchars, Lucy Atkinson, Ruth E. Brooke, Hanny Musa, Carol J. Milligan, Trevor F C Batten, Noel J. Buckley, Simon H. Parson, Jim Deuchars

Research output: Contribution to journalArticlepeer-review

263 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)7143-7152
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number18
DOIs
Publication statusPublished - 15 Sep 2001
Externally publishedYes

Keywords

  • ATP
  • Excitatory amino acid transmission
  • Medulla oblongata
  • Neuromuscular junction
  • Purine receptor
  • Spinal cord
  • Synaptic transmission

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