P2X receptors mediate AMPA receptor function in hippocampal neurons
ATP activated postsynaptic P2X receptors (P2XRs) have been shown to decrease the amplitude of miniature excitatory postsynaptic currents and AMPA-evoked currents in hippocampal neurons, in a paper recently published in the journal Neuron. This can happen through activation of P2XRs by exogenous ATP or noradrenaline-dependent glial release of endogenous ATP.
The study, supervised by Dr Eric Boué-Grabot at the CNRS Institut des Maladies Neurodégenératives, also found that P2X2Rs trigger internalisation of AMPA receptors (AMPARs) reducing the number of AMPARs on dendrites and at synapses. These findings show P2XRs ability to regulate synaptic strength in the hippocampus.
P2X receptors are ATP-gated cation channels and several subtypes are expressed widely across different brain regions. Each subtype is a potentially interesting target for pharmacological intervention. Recently discovered or synthesised molecular agonists and antagonists may be able to treat diseases as diverse as rheumatoid arthritis, multiple sclerosis, spinal cord injury and bladder dysfunction.
This research has helped to generate new knowledge of how P2XRs function within brain synapses furthering our understanding of their neuromodulatory role. These findings should help to further the search for pharmacologically useful drugs to treat a number of brain dysfunctions.
Electrophysiological experiments conducted for this paper were carried out on a Scientifica SliceScope Pro 2000 system. Dr Estelle Toulme told us this equipment was very stable and user friendly allowing the researchers to gather data quickly.
Pougnet J.T., Toulme E., Martinez A., Choquet D., Hosy E., Boué-Grabot R. (2014) ATP P2X Receptors Downregulate AMPA Receptor Trafficking and Postsynaptic Efficacy in Hippocampal Neurons Neuron, 83;417-430 doi: 10.1016/j.neuron.2014.06.005