Autocrine boost of NMDAR current in hippocampal CA1 pyramidal neurons by a PMCA-dependent, perisynaptic, extracellular pH shift

The plasma membrane Ca(2+)-ATPase (PMCA) is found near postsynaptic NMDARs. This transporter is a Ca(2+)-H(+) exchanger that raises cell surface pH. We tested whether the PMCA acts in an autocrine fashion to boost pH-sensitive, postsynaptic NMDAR currents. In mouse hippocampal slices, NMDAR EPSCs in...

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Bibliographic Details
Published in:The Journal of neuroscience 2015-01, Vol.35 (3), p.873-877
Main Authors: Chen, Huei-Ying, Chesler, Mitchell
Format: Article
Language:English
Subjects:
Animals
Autocrine Communication - drug effects
Autocrine Communication - physiology
Benzolamide - pharmacology
Brief Communications
CA1 Region, Hippocampal - drug effects
CA1 Region, Hippocampal - physiology
Carbonic Anhydrases - pharmacology
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
Female
Hydrogen-Ion Concentration
Male
Mice
Plasma Membrane Calcium-Transporting ATPases - metabolism
Pyramidal Cells - drug effects
Pyramidal Cells - physiology
Receptors, N-Methyl-D-Aspartate - metabolism
Synapses - drug effects
Synapses - physiology
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Summary:The plasma membrane Ca(2+)-ATPase (PMCA) is found near postsynaptic NMDARs. This transporter is a Ca(2+)-H(+) exchanger that raises cell surface pH. We tested whether the PMCA acts in an autocrine fashion to boost pH-sensitive, postsynaptic NMDAR currents. In mouse hippocampal slices, NMDAR EPSCs in a singly activated CA1 pyramidal neuron were reduced when buffering was augmented by exogenous carbonic anhydrase (XCAR). This effect was blocked by the enzyme inhibitor benzolamide and mimicked by the addition of HEPES buffer. Similar EPSC reduction occurred when PMCA activation was prevented by dialysis of BAPTA or the PMCA inhibitor carboxyeosin. Using HEPES, BAPTA, or carboxyeosin, the effect of XCAR was completely occluded. XCAR similarly curtailed NMDAR EPSCs of minimal amplitude, but had no effect on small AMPAR responses. These results indicate that a significant fraction of the postsynaptic NMDAR current is reliant on a perisynaptic extracellular alkaline shift generated by the PMCA.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.2293-14.2015