ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2014
Effects of metabolic acidosis on intracellular pH responses in multiple cell types.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Human Plastins are Novel Cytoskeletal pH Sensors with a Reduced F-actin Bundling Capacity at Basic pH.Journal of molecular biology · 2025Article
- Association between delta anion gap/delta bicarbonate and outcome of surgical patients admitted to intensive care unit.BMC anesthesiology · 2024Observational
- Primary Distal Renal Tubular Acidosis: Toward an Optimal Correction of Metabolic Acidosis.Clinical journal of the American Society of Nephrology : CJASN · 2024Review
- Effects of extracellular metabolic acidosis and out-of-equilibrium COFrontiers in physiology · 2024Article
- Effects of extracellular metabolic acidosis on the homeostasis of intracellular pH in hippocampal neurons.Frontiers in physiology · 2024Article
- Novel RPTPγ and RPTPζ splice variants from mixed neuron-astrocyte hippocampal cultures as well as from the hippocampi of newborn and adult mice.Frontiers in physiology · 2024Article
- Article
- Carbonic anhydrase and soluble adenylate cyclase regulation of cystic fibrosis cellular phenotypes.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Proton Quantum Tunneling: Influence and Relevance to Acidosis-Induced Cardiac Arrhythmias/Cardiac Arrest.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Article
- COInterface focus · 2021Review
- NLRP3 Inflammasome: Potential Role in Obesity Related Low-Grade Inflammation and Insulin Resistance in Skeletal Muscle.International journal of molecular sciences · 2021Review
- The therapeutic importance of acid-base balance.Biochemical pharmacology · 2021Review
- The Molecular Effects of Dietary Acid Load on Metabolic Disease (The Cellular PasaDoble: The Fast-Paced Dance of pH Regulation).Frontiers in molecular medicine · 2021Review
- KD025 Shifts Pulmonary Endothelial Cell Bioenergetics and Decreases Baseline Lung Permeability.American journal of respiratory cell and molecular biology · 2020Article
- Extrinsic acidosis suppresses glycolysis and migration while increasing network formation in pulmonary microvascular endothelial cells.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- The Natural Compound Climacostol as a Prodrug Strategy Based on pH Activation for Efficient Delivery of Cytotoxic Small Agents.Frontiers in chemistry · 2019Article
- Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Bicarbonate sensing in mouse cortical astrocytes during extracellular acid/base disturbances.The Journal of physiology · 2017Article
- Role of ClThe Journal of physiology · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Metabolic acidosis (MAc), a decrease in extracellular pH (pHo) caused by a decrease in [HCO3 (-)]o at a fixed [CO2]o, is a common clinical condition and causes intracellular pH (pHi) to fall. Although previous work has suggested that MAc-induced decreases in pHi (ΔpHi) differ among cell types, what is not clear is the extent to which these differences are the result of the wide variety of methodologies employed by various investigators. In the present study, we evaluated the effects of two sequential MAc challenges (MAc1 and MAc2) on pHi in 10 cell types/lines: primary-cultured hippocampal (HCN) neurons and astrocytes (HCA), primary-cultured medullary raphé (MRN) neurons, and astrocytes (MRA), CT26 colon cancer, the C2C12 skeletal muscles, primary-cultured bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC), Ink4a/ARF-null melanocytes, and XB-2 keratinocytes. We monitor pHi using ratiometric fluorescence imaging of 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein while imposing MAc: lowering (pHo) from 7.4 to 7.2 by decreasing [HCO3 (-)]o from 22 to 14 mM at 5% CO2 for 7 min. After MAc1, we return cells to the control solution for 10 min and impose MAc2. Using our definition of MAc resistance [(ΔpHi/ΔpHo) ≤ 40%], during MAc1, ∼70% of CT26 and ∼50% of C2C12 are MAc-resistant, whereas the other cell types are predominantly MAc-sensitive. During MAc2, some cells adapt [(ΔpHi/ΔpHo)2 < (ΔpHi/ΔpHo)1], particularly HCA, C2C12, and BMDC. Most maintain consistent responses [(ΔpHi/ΔpHo)2 ≅ (ΔpHi/ΔpHo)1], and a few decompensate [(ΔpHi/ΔpHo)2>(ΔpHi/ΔpHo)1], particularly HCN, C2C12, and XB-2. Thus, responses to twin MAc challenges depend both on the individual cell and cell type.
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Registered trials
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