ArticleThe Journal of biological chemistry2014
Function and regulation of the Na+-Ca2+ exchanger NCX3 splice variants in brain and skeletal muscle.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- The NaThe Journal of veterinary medical science · 2026Review
- Nonthermal radiofrequency radiation promotes hematopoietic stem and progenitor cells function by regulating CaStem cell research & therapy · 2026Article
- The Molecular Biology of Placental Transport of Calcium to the Human Foetus.International journal of molecular sciences · 2025Review
- Structural dynamics of NaCommunications biology · 2024Article
- Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System.International journal of molecular sciences · 2023Review
- Genetic architecture for skeletal muscle glycolytic potential in Chinese Erhualian pigs revealed by a genome-wide association study using 1.4M SNP array.Frontiers in genetics · 2023Article
- Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.Neuron · 2022Article
- Disturbance of calcium homeostasis and myogenesis caused by TET2 deletion in muscle stem cells.Cell death discovery · 2022Article
- The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites.Biomolecules · 2022Review
- Induced pluripotent stem cells as a platform to understand patient-specific responses to opioids and anaesthetics.British journal of pharmacology · 2020Review
- Sodium-Calcium Exchangers of the SLC8 Family in Oligodendrocytes: Functional Properties in Health and Disease.Neurochemical research · 2020Review
- TGF-β Signaling Regulates SLC8A3 Expression and Prevents Oxidative Stress in Developing Midbrain Dopaminergic and Dorsal Raphe Serotonergic Neurons.International journal of molecular sciences · 2020Article
- Alternative splicing isoforms in health and disease.Pflugers Archiv : European journal of physiology · 2018Review
- Hypoxia Mimetic Agents for Ischemic Stroke.Frontiers in cell and developmental biology · 2018Review
- Structure-based dynamic arrays in regulatory domains of sodium-calcium exchanger (NCX) isoforms.Scientific reports · 2017Article
- Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na⁺/Ca²⁺ exchanger.Scientific reports · 2016Article
- Calpain-3-mediated regulation of the Na⁺-Ca²⁺ exchanger isoform 3.Pflugers Archiv : European journal of physiology · 2016Article
- The role of Na+/Ca2+ exchanger subtypes in neuronal ischemic injury.Translational stroke research · 2015Review
- Expression of calcium-buffering proteins in rat intrinsic laryngeal muscles.Physiological reports · 2015Article
- The properties, distribution and function of Na(+)-Ca(2+) exchanger isoforms in rat cutaneous sensory neurons.The Journal of physiology · 2014Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Isoform 3 of the Na(+)-Ca(2+) exchanger (NCX3) is crucial for maintaining intracellular calcium ([Ca(2+)]i) homeostasis in excitable tissues. In this sense NCX3 plays a key role in neuronal excitotoxicity and Ca(2+) extrusion during skeletal muscle relaxation. Alternative splicing generates two variants (NCX3-AC and NCX3-B). Here, we demonstrated that NCX3 variants display a tissue-specific distribution in mice, with NCX3-B as mostly expressed in brain and NCX-AC as predominant in skeletal muscle. Using Fura-2-based Ca(2+) imaging, we measured the capacity and regulation of the two variants during Ca(2+) extrusion and uptake in different conditions. Functional studies revealed that, although both variants are activated by intracellular sodium ([Na(+)]i), NCX3-AC has a higher [Na(+)]i sensitivity, as Ca(2+) influx is observed in the presence of extracellular Na(+). This effect could be partially mimicked for NCX3-B by mutating several glutamate residues in its cytoplasmic loop. In addition, NCX3-AC displayed a higher capacity of both Ca(2+) extrusion and uptake compared with NCX3-B, together with an increased sensitivity to intracellular Ca(2+). Strikingly, substitution of Glu(580) in NCX3-B with its NCX3-AC equivalent Lys(580) recapitulated the functional properties of NCX3-AC regarding Ca(2+) sensitivity, Lys(580) presumably acting through a structure stabilization of the Ca(2+) binding site. The higher Ca(2+) uptake capacity of NCX3-AC compared with NCX3-B is in line with the necessity to restore Ca(2+) levels in the sarcoplasmic reticulum during prolonged exercise. The latter result, consistent with the high expression in the slow-twitch muscle, suggests that this variant may contribute to the Ca(2+) handling beyond that of extruding Ca(2+).
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