title: Role of P2X4 receptors in synaptic strengthening in mouse CA1 hippocampal neurons.
abstract: P2X4 receptors are calcium-permeable cation channels gated by extracellular ATP. They are found close to subsynaptic sites on hippocampal CA1 neurons. We compared features of synaptic strengthening between wild-type and P2X4 knockout mice (21-26 days old). Potentiation evoked by a tetanic presynaptic stimulus (100 Hz, 1 s) paired with postsynaptic depolarization was less in P2X4(-/-) mice than in wild-type mice (230 vs. 50% potentiation). Paired-pulse ratios and the amplitude and frequency of spontaneous excitatory postsynaptic currents (EPSCs) were not different between wild-type and knockout mice. Prior hyperpolarization (ten 3 s pulses to -120 mV at 0.17 Hz) potentiated the amplitude of spontaneous EPSCs in wild-type mice, but not in P2X4(-/-) mice; this potentiation was not affected by nifedipine, but was abolished by 10 mM 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA) in the recording pipette. The amplitude of N-methyl-d-aspartate EPSCs (in 6-cyano-7-nitroquinoxaline-2,3-dione, 10 or 30 μm, at -100 mV) facilitated during 20 min recording in magnesium-free solution. In wild-type mice, this facilitation of the N-methyl-d-aspartate EPSC was reduced by about 50% by intracellular BAPTA (10 mM), ifenprodil (3 μm) or 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)1H-imidazole (5 μm). In P2X4(-/-) mice, the facilitation was much less, and was unaffected by intracellular BAPTA, ifenprodil (3 μm) or mitogen-activated protein (MAP) kinase inhibitor 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)1H-imidazole (5 μm). This suggests that the absence of P2X4 receptors limits the incorporation of NR2B subunits into synaptic N-methyl-d-aspartate receptors.
authors.affiliation: Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Baxter
authors.forename: Se Joon
authors.initials: SJ
authors.lastname: Choi
authors.forename: Joan A
authors.initials: JA
authors.lastname: Sim
authors.forename: R Alan
authors.initials: RA
authors.lastname: North
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D058848:Receptors, Purinergic P2X4 / Q000235:genetics / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D058848:Receptors, Purinergic P2X4; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D004533:Egtazic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid