Present address: Evotec AG, Schnakenburgallee 114, 22525 Hamburg, Germany.
Role of P2X4 receptors in synaptic strengthening in mouse CA1 hippocampal neurons
Article first published online: 12 JUL 2011
© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 34, Issue 2, pages 213–220, July 2011
How to Cite
Baxter, A. W., Choi, S. J., Sim, J. A. and North, R. A. (2011), Role of P2X4 receptors in synaptic strengthening in mouse CA1 hippocampal neurons. European Journal of Neuroscience, 34: 213–220. doi: 10.1111/j.1460-9568.2011.07763.x
- Issue published online: 18 JUL 2011
- Article first published online: 12 JUL 2011
- Received 26 April 2011, revised 10 May 2011, accepted 12 May 2011
- brain slice;
- NR2B receptors;
- P2X4 receptors;
- whole-cell recording
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.