ArticleThe Journal of physiology2013
Sarcolemmal localisation of Na+/H+ exchange and Na+-HCO3- co-transport influences the spatial regulation of intracellular pH in rat ventricular myocytes.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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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
34 citing papers in PubMed, 56 citations in OpenAlex.
- SLC4A7/NBCn1 maintains intracellular pH to support mTORC1 activity and antibody-secreting cell differentiation.Nature communications · 2026Article
- A novel transgenic reporter of extracellular acidification in zebrafish elucidates skeletal muscle T-tubule pH regulation.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Loss of NaActa physiologica (Oxford, England) · 2025Article
- Cardioprotection and neurobehavioral impact of swimming training in ovariectomized rats.GeroScience · 2025Article
- Inhibition of Sodium/Hydrogen Exchanger-1 in the Right Ventricle and Lung Dysfunction Induced by Experimental Pulmonary Arterial Hypertension in Rats.Journal of the American Heart Association · 2025Article
- Potential Theranostic Roles of SLC4 Molecules in Human Diseases.International journal of molecular sciences · 2023Review
- Understanding the Physiological Role of Electroneutral NaPharmaceuticals (Basel, Switzerland) · 2022Review
- The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes.The Journal of physiology · 2022Article
- Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia-reperfusion.Physiological reports · 2021Article
- Acidosis modifies effects of phosphorylated tropomyosin on the actin-myosin interaction in the myocardium.Journal of muscle research and cell motility · 2021Article
- Carbonic anhydrases enhance activity of endogenous Na-H exchangers and not the electrogenic Na/HCOThe Journal of physiology · 2020Article
- The Fundamental Role of Bicarbonate Transporters and Associated Carbonic Anhydrase Enzymes in Maintaining Ion and pH Homeostasis in Non-Secretory Organs.International journal of molecular sciences · 2020Review
- Cardiomyocyte NaFrontiers in cardiovascular medicine · 2020Article
- Disruption of Transverse-Tubules Eliminates the Slow Force Response to Stretch in Isolated Rat Trabeculae.Frontiers in physiology · 2020Article
- The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility.Pflugers Archiv : European journal of physiology · 2020Article
- A stochastic model of ion channel cluster formation in the plasma membrane.The Journal of general physiology · 2019Article
- A high-throughput ratiometric method for imaging hypertrophic growth in cultured primary cardiac myocytes.Journal of molecular and cellular cardiology · 2019Article
- Regulation of Intracellular pH is Altered in Cardiac Myocytes of Ovariectomized Rats.Journal of the American Heart Association · 2019Article
- NBCe1 NaWorld journal of cardiology · 2018Article
- The ins and outs of acid-base transport in skeletal muscle.The Journal of general physiology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Membrane acid extrusion by Na(+)/H(+) exchange (NHE1) and Na(+)-HCO3(-) co-transport (NBC) is essential for maintaining a low cytoplasmic [H(+)] (∼60 nm, equivalent to an intracellular pH (pHi) of 7.2). This protects myocardial function from the high chemical reactivity of H(+) ions, universal end-products of metabolism. We show here that, in rat ventricular myocytes, fluorescent antibodies map the NBC isoforms NBCe1 and NBCn1 to lateral sarcolemma, intercalated discs and transverse tubules (t-tubules), while NHE1 is absent from t-tubules. This unexpected difference matches functional measurements of pHi regulation (using AM-loaded SNARF-1, a pH fluorophore). Thus, myocyte detubulation (by transient exposure to 1.5 m formamide) reduces global acid extrusion on NBC by 40%, without affecting NHE1. Similarly, confocal pHi imaging reveals that NBC stimulation induces spatially uniform pHi recovery from acidosis, whereas NHE1 stimulation induces pHi non-uniformity during recovery (of ∼0.1 units, for 2-3 min), particularly at the ends of the cell where intercalated discs are commonly located, and where NHE1 immunostaining is prominent. Mathematical modelling shows that this induction of local pHi microdomains is favoured by low cytoplasmic H(+) mobility and long H(+) diffusion distances, particularly to surface NHE1 transporters mediating high membrane flux. Our results provide the first evidence for a spatial localisation of [H(+)]i regulation in ventricular myocytes, suggesting that, by guarding pHi, NHE1 preferentially protects gap junctional communication at intercalated discs, while NBC locally protects t-tubular excitation-contraction coupling.
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Registered trials
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.