title: Autocrine boost of NMDAR current in hippocampal CA1 pyramidal neurons by a PMCA-dependent, perisynaptic, extracellular pH shift.
abstract: 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.
authors.affiliation: Department of Neuroscience and Physiology and.
authors.forename: Huei-Ying
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Neuroscience and Physiology and Department of Neurosurgery, New York University School of Medicine, New York, New York 10016 Mitchell.Chesler@nyumc.org.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Chesler
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology*; D001574:Benzolamide / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D002256:Carbonic Anhydrases / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D053499:Plasma Membrane Calcium-Transporting ATPases; D002256:Carbonic Anhydrases; D001574:Benzolamide
keywords: CA1; Ca2+ ATPase; benzolamide; carbonic anhydrase; carboxyeosin; hippocampus