Evidence map›Paper›PMID 19939954›Full record

ArticleJournal of neurophysiology2010

Rapid rise of extracellular pH evoked by neural activity is generated by the plasma membrane calcium ATPase.

Sachin Makani, Mitchell Chesler

Abstract read
In one paragraph

Article in Journal of neurophysiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
1.1field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 68 citations in OpenAlex.

  1. Acid-sensing ion channels as sensors of brain metabolic state.Pflugers Archiv : European journal of physiology · 2026
    Review
  2. Article
  3. Article
  4. A dangerous liaison: Spreading depolarization and tissue acidification in cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025
    Review
  5. Article
  6. Review
  7. Postsynaptic Calcium Extrusion at the Mouse Neuromuscular Junction Alkalinizes the Synaptic Cleft.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Plasma Membrane CaBiomolecules · 2021
    Article
  12. Article
  13. Molecular mechanisms of brain water transport.Nature reviews. Neuroscience · 2021
    Review
  14. Article
  15. The therapeutic importance of acid-base balance.Biochemical pharmacology · 2021
    Review
  16. Changes in HFrontiers in cellular neuroscience · 2021
    Article
  17. Article
  18. Neurovascular Coupling in Development and Disease: Focus on Astrocytes.Frontiers in cell and developmental biology · 2021
    Review
  19. Alkalinization of the Synaptic Cleft during Excitatory Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  20. Neuronal Glutamatergic Synaptic Clefts Alkalinize Rather Than Acidify during Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Sachin MakaniDepartment of Physiology and Neuroscience, New York University Langone Medical Center, New York, New York 10016, USA.
Mitchell Chesler
NYU Langone Health · US

Funding

Dynamics of pH Regulation in the BrainR01NS032123 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHESLER, MITCHELL · 1993 to 2018
$6.3M
Regulation and Modulation of Postysynaptic NMDA Receptors by Extracellular pHF31NS058152 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MAKANI, SACHIN · 2007 to 2009
$60k
NINDS NIH HHS F31 NS-058152NINDS NIH HHS R01 NS-032123
6 · The paper itself

Abstract

In hippocampus, synchronous activation of CA1 pyramidal neurons causes a rapid, extracellular, population alkaline transient (PAT). It has been suggested that the plasma membrane Ca(2+)-ATPase (PMCA) is the source of this alkalinization, because it exchanges cytosolic Ca(2+) for external H(+). Evidence supporting this hypothesis, however, has thus far been inconclusive. We addressed this long-standing problem by measuring surface alkaline transients (SATs) from voltage-clamped CA1 pyramidal neurons in juvenile mouse hippocampal slices, using concentric (high-speed, low-noise) pH microelectrodes placed against the somata. In saline containing benzolamide (a poorly permeant carbonic anhydrase blocker), a 2-s step from -60 to 0 mV caused a mean SAT of 0.02 unit pH. Addition of 5 mM HEPES to the artificial cerebrospinal fluid diminished the SAT by 91%. Nifedipine reduced the SAT by 53%. Removal of Ca(2+) from the saline abolished the SAT, and addition of BAPTA to the patch pipette reduced it by 79%. The inclusion of carboxyeosin (a PMCA inhibitor) in the pipette abolished the SAT, whether it was induced by a depolarizing step, or by simulated, repetitive, antidromic firing. The peak amplitude of the "antidromic" SAT of a single cell averaged 11% of the PAT elicited by comparable real antidromic activation of the CA1 neuronal population. Caloxin 2A1, an extracellular PMCA peptide inhibitor, blocked both the SAT and PAT by 42%. These results provide the first direct evidence that the PMCA can explain the extracellular alkaline shift elicited by synchronous firing.

Indexed as

Action PotentialsAnimalsCell MembraneCells, CulturedExtracellular FluidFemaleHydrogen-Ion ConcentrationMaleMicePlasma Membrane Calcium-Transporting ATPasesPyramidal CellsPlasma Membrane Calcium-Transporting ATPases

Identifiers

PMID19939954
PMCPMC2822688
OpenAlexW2075238065

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.