ArticleThe Journal of biological chemistry2013
Splice cassette II of Na+,HCO3(-) cotransporter NBCn1 (slc4a7) interacts with calcineurin A: implications for transporter activity and intracellular pH control during rat artery contractions.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Pooled it
- Pressure-Induced Changes in Intracellular pH Facilitate the Myogenic Response of Rat Small Tail Arteries.Acta physiologica (Oxford, England) · 2026Article
- Loss of NaActa physiologica (Oxford, England) · 2025Article
- Lactate orchestrates metabolic hemodynamic adaptations through a unique combination of venocontraction, artery relaxation, and positive inotropy.Acta physiologica (Oxford, England) · 2025Article
- Strengthening the basics: acids and bases influence vascular structure and function, tissue perfusion, blood pressure, and human cardiovascular disease.Pflugers Archiv : European journal of physiology · 2024Review
- The role of NaPflugers Archiv : European journal of physiology · 2024Review
- Calcineurin Is a Universal Regulator of Vessel Function-Focus on Vascular Smooth Muscle Cells.Cells · 2023Review
- Understanding the Physiological Role of Electroneutral NaPharmaceuticals (Basel, Switzerland) · 2022Review
- Ion Channels, Transporters, and Sensors Interact with the Acidic Tumor Microenvironment to Modify Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Article
- 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
- Acid-base regulation and sensing: Accelerators and brakes in metabolic regulation of cerebrovascular tone.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Review
- Had1 Is Required for Cell Wall Integrity and Fungal Virulence inG3 (Bethesda, Md.) · 2018Article
- Functions of intrinsic disorder in transmembrane proteins.Cellular and molecular life sciences : CMLS · 2017Review
- Increased NBCn1 expression, Na+/HCO3- co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension.Human molecular genetics · 2017Article
- Alternative transcription of sodium/bicarbonate transporter SLC4A7 gene enhanced by single nucleotide polymorphisms.Physiological genomics · 2017Article
- Rapid Action of Aldosterone on Protein Levels of Sodium-Hydrogen Exchangers and Protein Kinase C Beta Isoforms in Rat Kidney.International journal of endocrinology · 2017Article
- Extracellular HCO3- is sensed by mouse cerebral arteries: Regulation of tone by receptor protein tyrosine phosphatase γ.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Article
- Effects of Nt-truncation and coexpression of isolated Nt domains on the membrane trafficking of electroneutral Na+/HCO3- cotransporters.Scientific reports · 2015Article
- Structure and Function of SLC4 Family [Formula: see text] Transporters.Frontiers in physiology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of Na(+),HCO3(-) cotransport in vascular smooth muscle cells (VSMCs) contributes to intracellular pH (pH(i)) control during artery contraction, but the signaling pathways involved have been unknown. We investigated whether physical and functional interactions between the Na(+),HCO3(-) cotransporter NBCn1 (slc4a7) and the Ca(2+)/calmodulin-activated serine/threonine phosphatase calcineurin exist and play a role for pHi control in VSMCs. Using a yeast two-hybrid screen, we found that splice cassette II from the N terminus of NBCn1 interacts with calcineurin Aβ. When cassette II was truncated or mutated to disrupt the putative calcineurin binding motif PTVVIH, the interaction was abolished. Native NBCn1 and calcineurin Aβ co-immunoprecipitated from A7r5 rat VSMCs. A peptide (acetyl-DDIPTVVIH-amide), which mimics the putative calcineurin binding motif, inhibited the co-immunoprecipitation whereas a mutated peptide (acetyl-DDIATAVAA-amide) did not. Na(+),HCO3(-) cotransport activity was investigated in VSMCs of mesenteric arteries after an NH4(+) prepulse. During depolarization with 50 mM extracellular K(+) to raise intracellular [Ca(2+)], Na(+),HCO3(-) cotransport activity was inhibited 20-30% by calcineurin inhibitors (FK506 and cyclosporine A). FK506 did not affect Na(+),HCO3(-) cotransport activity in VSMCs when cytosolic [Ca(2+)] was lowered by buffering, nor did it disrupt binding between NBCn1 and calcineurin Aβ. FK506 augmented the intracellular acidification of VSMCs during norepinephrine-induced artery contractions. No physical or functional interactions between calcineurin Aβ and the Na(+)/H(+) exchanger NHE1 were observed in VSMCs. In conclusion, we demonstrate a physical interaction between calcineurin Aβ and cassette II of NBCn1. Intracellular Ca(2+) activates Na(+),HCO3(-) cotransport activity in VSMCs in a calcineurin-dependent manner which is important for protection against intracellular acidification.
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Registered trials
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