ArticleProceedings of the National Academy of Sciences of the United States of America2013
Coupled Ca2+/H+ transport by cytoplasmic buffers regulates local Ca2+ and H+ ion signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.
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- Nutritional Strategies for Optimizing Health, Sports Performance, and Recovery for Female Athletes and Other Physically Active Women: A Systematic Review.Nutrition reviews · 2025Pooled it
- Acute ketone monoester ingestion lowers resting cerebral blood flow: a randomized cross-over trial.The Journal of physiology · 2026Trial
- Effect of high-dose β-Alanine supplementation on uphill cycling performance in World Tour cyclists: A randomised controlled trial.PloS one · 2024Trial
- β-alanine supplementation improves in-vivo fresh and fatigued skeletal muscle relaxation speed.European journal of applied physiology · 2017Trial
- Effects of Four Weeks of β-Alanine Supplementation on Repeated Sprint Ability in Water Polo Players.PloS one · 2016Trial
- Review
- CaBiomolecules · 2025Review
- A comprehensive review on physiological and biological activities of carnosine: turning from preclinical facts to potential clinical applications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Cell cycle arrest of cardiomyocytes in the context of cardiac regeneration.Frontiers in cardiovascular medicine · 2025Review
- pH-regulated single cell migration.Pflugers Archiv : European journal of physiology · 2024Review
- Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation.Nature cardiovascular research · 2023Article
- The Anti-Cancer Activity of the Naturally Occurring Dipeptide Carnosine: Potential for Breast Cancer.Cells · 2023Review
- Physiology of intracellular calcium buffering.Physiological reviews · 2023Review
- The Therapeutic Potential of Novel Carnosine Formulations: Perspectives for Drug Development.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The Effect of β-Alanine Supplementation on Performance, Cognitive Function and Resiliency in Soldiers.Nutrients · 2023Review
- Physiological Roles of Carnosine in Myocardial Function and Health.Advances in nutrition (Bethesda, Md.) · 2022Review
- Dietary Supplement Use of Turkish Footballers: Differences by Sex and Competition Level.Nutrients · 2022Article
- The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes.The Journal of physiology · 2022Article
- Meat intake and risk of mortality and graft failure in kidney transplant recipients.The American journal of clinical nutrition · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Ca(2+) signaling regulates cell function. This is subject to modulation by H(+) ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca(2+)] ([Ca(2+)]i) or [H(+)] ([H(+)]i) can become compartmentalized, leading potentially to complex spatial Ca(2+)/H(+) coupling. This was studied by fluorescence imaging of cardiac myocytes. An increase in [H(+)]i, produced by superfusion of acetate (salt of membrane-permeant weak acid), evoked a [Ca(2+)]i rise, independent of sarcolemmal Ca(2+) influx or release from mitochondria, sarcoplasmic reticulum, or acidic stores. Photolytic H(+) uncaging from 2-nitrobenzaldehyde also raised [Ca(2+)]i, and the yield was reduced following inhibition of glycolysis or mitochondrial respiration. H(+) uncaging into buffer mixtures in vitro demonstrated that Ca(2+) unloading from proteins, histidyl dipeptides (HDPs; e.g., carnosine), and ATP can underlie the H(+)-evoked [Ca(2+)]i rise. Raising [H(+)]i tonically at one end of a myocyte evoked a local [Ca(2+)]i rise in the acidic microdomain, which did not dissipate. The result is consistent with uphill Ca(2+) transport into the acidic zone via Ca(2+)/H(+) exchange on diffusible HDPs and ATP molecules, energized by the [H(+)]i gradient. Ca(2+) recruitment to a localized acid microdomain was greatly reduced during intracellular Mg(2+) overload or by ATP depletion, maneuvers that reduce the Ca(2+)-carrying capacity of HDPs. Cytoplasmic HDPs and ATP underlie spatial Ca(2+)/H(+) coupling in the cardiac myocyte by providing ion exchange and transport on common buffer sites. Given the abundance of cellular HDPs and ATP, spatial Ca(2+)/H(+) coupling is likely to be of general importance in cell signaling.
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Registered trials
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