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Brief Communications

Autocrine Boost of NMDAR Current in Hippocampal CA1 Pyramidal Neurons by a PMCA-Dependent, Perisynaptic, Extracellular pH Shift

Huei-Ying Chen and Mitchell Chesler
Journal of Neuroscience 21 January 2015, 35 (3) 873-877; https://doi.org/10.1523/JNEUROSCI.2293-14.2015
Huei-Ying Chen
1Department of Neuroscience and Physiology and
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Mitchell Chesler
1Department of Neuroscience and Physiology and
2Department of Neurosurgery, New York University School of Medicine, New York, New York 10016
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    Figure 1.

    XCAR reduced NMDAR-mediated EPSCs. a, EPSC in XCAR (red) was reduced compared with control (CTL) at a VH of +50 mV. Scaled trace (green) shows no effect on time course. b, Effect of XCAR on peak EPSC in 9 cells. Dashed lines indicate use of human, recombinant type IV carbonic anhydrase in 3 cells. c, XCAR reduced charge transfer. d, Half-time of decay was unaffected by XCAR. e, XCAR had no effect on the EPSC reversal potential. f, Averaged EPSCs at 5–10 minutes (black) versus 17–22 minutes (delay, red) after breakthrough. g, Peak EPSC of 5 cells in delay experiments. h, XCAR had no effect on peak EPSC in presence of benzolamide. I, Peak EPSC in 6 cells exposed to XCAR in the presence of benzolamide. Calibrations: 100 pA/50 ms. VH = +50 mV for a–d and f–i.

  • Figure 2.
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    Figure 2.

    Effect of XCAR was not voltage dependent. a, EPSC curtailed by XCAR (VH = −30 mV.) b, XCAR reduced EPSC amplitude in 5 cells (VH = −30 mV). c, XCAR reduced the EPSC after dialysis of d-890 (VH = +50 mV). d, Reduction of EPSC by XCAR in 5 cells after dialysis of d-890 (VH = +50 mV) e, XCAR reduction of EPSC after dialysis of d-890 (VH = −30 mV). f, Reduction of EPSC by XCAR in 5 cells after dialysis of d-890 (VH = −30 mV). Calibration: 100 pA/50 ms.

  • Figure 3.
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    Figure 3.

    XCAR effect was due to buffering and required the PMCA. a, EPSC reduced by 20 mm HEPES. b, Effect of HEPES in 5 cells. c, In 20 mm HEPES, XCAR had no effect on the EPSC. d, EPSC peak from 5 cells exposed to XCAR in 20 mm HEPES. e, Peak EPSC was reduced by dialysis of BAPTA. f, Effect of BAPTA on peak EPSC in 7 cells. g, After dialysis of BAPTA for 10 minutes, XCAR had no effect on the peak EPSC. h, Peak EPSC before and after XCAR in 5 cells dialyzed with BAPTA. i, Peak EPSC was reduced by dialysis of CE. j, Effect of CE on peak EPSC in 7 cells. k, After dialysis of CE, exposure to XCAR had no effect on peak EPSC. l, Peak EPSC before and after XCAR in 5 cells dialyzed with CE. VH = +50 mV for a–l. Calibration: 100 pA/50 ms. For e, f and I, j, the data were compared at 3–8 minutes versus 12–17 minutes after breakthrough.

  • Figure 4.
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    Figure 4.

    Small NMDAR EPSCs reduced by XCAR. a, Small EPSC curtailed by XCAR. b, Effect of XCAR on small EPSCs in 9 cells. c, Small EPSC recorded 5–10 minutes (CTL, black) versus 17–22 minutes after breakthrough (Delay, red). d, Peak EPSC in 5 delay experiments. e, XCAR had no effect on AMPAR peak EPSC (no DNQX, VH = −70 mV). f, Effect of XCAR on peak of small, AMPAR EPSCs in 5 cells. VH = +50 mV for a–d. Calibration: 20 pA/20 ms (a,c), 20 pA/10 ms (e).

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The Journal of Neuroscience: 35 (3)
Journal of Neuroscience
Vol. 35, Issue 3
21 Jan 2015
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Autocrine Boost of NMDAR Current in Hippocampal CA1 Pyramidal Neurons by a PMCA-Dependent, Perisynaptic, Extracellular pH Shift
Huei-Ying Chen, Mitchell Chesler
Journal of Neuroscience 21 January 2015, 35 (3) 873-877; DOI: 10.1523/JNEUROSCI.2293-14.2015

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Autocrine Boost of NMDAR Current in Hippocampal CA1 Pyramidal Neurons by a PMCA-Dependent, Perisynaptic, Extracellular pH Shift
Huei-Ying Chen, Mitchell Chesler
Journal of Neuroscience 21 January 2015, 35 (3) 873-877; DOI: 10.1523/JNEUROSCI.2293-14.2015
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Keywords

  • benzolamide
  • CA1
  • Ca2+ ATPase
  • carbonic anhydrase
  • carboxyeosin
  • hippocampus

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