title: NMDA receptor-dependent afterdepolarizations are curtailed by carbonic anhydrase 14: regulation of a short-term postsynaptic potentiation.
abstract: In the hippocampus, extracellular carbonic anhydrase (Car) speeds the buffering of an activity-generated rise in extracellular pH that impacts H(+)-sensitive NMDA receptors (NMDARs). We studied the role of Car14 in this brain structure, in which it is expressed solely on neurons. Current-clamp responses were recorded from CA1 pyramidal neurons in wild-type (WT) versus Car14 knock-out (KO) mice 2 s before (control) and after (test) a 10 pulse, 100 Hz afferent train. In both WT and KO, the half-width (HW) of the test response, and its number of spikes, were augmented relative to the control. An increase in presynaptic release was not involved, because AMPAR-mediated EPSCs were depressed after a train. The increases in HW and spike number were both greater in the Car14 KO. In 0 Mg(2+) saline with picrotoxin (using a 20 Hz train), the HW measures were still greater in the KO. The Car inhibitor benzolamide (BZ) enhanced the test response HW in the WT but had no effect on the already-prolonged HW in the KO. With intracellular MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]-cyclohepten-5,10-imine maleate], the curtailed WT and KO responses were indistinguishable, and BZ caused no change. In contrast, the extracellular alkaline changes evoked by the train were not different between WT and KO, and BZ amplified these alkalinizations similarly. These data suggest that Car14 regulates pH transients in the perisynaptic microenvironment and govern their impact on NMDARs but plays little role in buffering pH shifts in the broader, macroscopic, extracellular space.
authors.affiliation: Departments of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Makani
authors.forename: Huei-Ying
authors.initials: HY
authors.lastname: Chen
authors.forename: Susana
authors.initials: S
authors.lastname: Esquenazi
authors.forename: Gul N
authors.initials: GN
authors.lastname: Shah
authors.forename: Abdul
authors.initials: A
authors.lastname: Waheed
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
authors.forename: Mitchell
authors.initials: M
authors.lastname: Chesler
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D003627:Data Interpretation, Statistical; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008839:Microelectrodes; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D001569:Benzodiazepines; D002256:Carbonic Anhydrases; D018756:GABA Antagonists; D018757:GABA Modulators; D008274:Magnesium; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; C466621:carbonic anhydrase XIV