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PMID: 11549725 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 18 ·2001-09-15 ·Pages 7143-52

Deuchars SA, Atkinson L, Brooke RE, Musa H, Milligan CJ, Batten TF, Buckley NJ, Parson SH, Deuchars J

Abstract

The ionotropic ATP receptor subunits P2X(1-6) receptors play important roles in synaptic transmission, yet the P2X(7) receptor has been reported as absent from neurons in the normal adult brain. Here we use RT-PCR to demonstrate that transcripts for the P2X(7) receptor are present in extracts from the medulla oblongata, spinal cord, and nodose ganglion. Using in situ hybridization mRNA encoding, the P2X(7) receptor was detected in numerous neurons throughout the medulla oblongata and spinal cord. Localizing the P2X(7) 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 microm) resulted in glutamate mediated excitation of recorded neurons, blocked by P2X(7) receptor antagonists oxidized ATP (100 microm) and Brilliant Blue G (2 microm). At the neuromuscular junction (NMJ) immunohistochemistry revealed that the P2X(7) 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 microm). This BzATP evoked destaining is blocked by oxidized ATP (100 microm) and Brilliant Blue G (1 microm). This indicates that activation of the P2X(7) 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.

MeSH Terms
Animals Central Nervous System/chemistry,cytology,metabolism Glutamic Acid/metabolism Immunohistochemistry In Situ Hybridization Male Medulla Oblongata/chemistry,cytology,metabolism Mice Mice, Inbred C57BL Muscle, Skeletal/innervation Neuromuscular Junction/metabolism Neurons/cytology,metabolism Neurotransmitter Agents/metabolism Nodose Ganglion/chemistry,cytology,metabolism Patch-Clamp Techniques Peripheral Nervous System/chemistry,cytology,metabolism Presynaptic Terminals/metabolism RNA, Messenger/analysis,biosynthesis Rats Rats, Wistar Receptors, Purinergic P2/genetics,metabolism Receptors, Purinergic P2X7 Reverse Transcriptase Polymerase Chain Reaction Spinal Cord/chemistry,cytology,metabolism Synaptic Transmission/physiology
Chemicals
Neurotransmitter Agents P2rx7 protein, mouse RNA, Messenger Receptors, Purinergic P2 Receptors, Purinergic P2X7 Glutamic Acid
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Deuchars S A
School of Biomedical Sciences, University of Leeds, LS2 9NQ, Leeds, United Kingdom. J.Deuchars@leeds.ac.uk
Atkinson L
Brooke R E
Musa H
Milligan C J
Batten T F
Buckley N J
Parson S H
Deuchars J
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
j.deuchars@leeds.ac.uk
Published
2001-09-15
Pages
7143-52
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762981
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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