ArticleJournal of neurophysiology2010
Rapid rise of extracellular pH evoked by neural activity is generated by the plasma membrane calcium ATPase.
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.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- Acid-sensing ion channels as sensors of brain metabolic state.Pflugers Archiv : European journal of physiology · 2026Review
- Differential synaptic depression mediates the therapeutic effect of deep brain stimulation.Nature neuroscience · 2025Article
- Dynamics of glia and neurons regulate homeostatic rest, sleep and feeding behavior in Drosophila.Nature neuroscience · 2025Article
- 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 · 2025Review
- Neurovascular coupling during hypercapnia in cerebral blood flow regulation.Nature communications · 2024Article
- pH regulating mechanisms of astrocytes: A critical component in physiology and disease of the brain.Cell calcium · 2024Review
- Postsynaptic Calcium Extrusion at the Mouse Neuromuscular Junction Alkalinizes the Synaptic Cleft.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- A genetically targeted ion sensor reveals distinct seizure-related chloride and pH dynamics in GABAergic interneuron populations.iScience · 2023Article
- The Reversal Characteristics of GABAergic Neurons: A Neurovascular Model.Journal of biomechanical engineering · 2023Article
- Computational modeling predicts ephemeral acidic microdomains in the glutamatergic synaptic cleft.Biophysical journal · 2021Article
- Plasma Membrane CaBiomolecules · 2021Article
- Spontaneous, synchronous zinc spikes oscillate with neural excitability and calcium spikes in primary hippocampal neuron culture.Journal of neurochemistry · 2021Article
- Molecular mechanisms of brain water transport.Nature reviews. Neuroscience · 2021Review
- Alkaline brain pH shift in rodent lithium-pilocarpine model of epilepsy with chronic seizures.Brain research · 2021Article
- The therapeutic importance of acid-base balance.Biochemical pharmacology · 2021Review
- Changes in HFrontiers in cellular neuroscience · 2021Article
- Review and Hypothesis: A Potential Common Link Between Glial Cells, Calcium Changes, Modulation of Synaptic Transmission, Spreading Depression, Migraine, and Epilepsy-HFrontiers in cellular neuroscience · 2021Article
- Neurovascular Coupling in Development and Disease: Focus on Astrocytes.Frontiers in cell and developmental biology · 2021Review
- Alkalinization of the Synaptic Cleft during Excitatory Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Neuronal Glutamatergic Synaptic Clefts Alkalinize Rather Than Acidify during Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
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.
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