ArticleProceedings of the National Academy of Sciences of the United States of America2013
The cardiac Na+-Ca2+ exchanger has two cytoplasmic ion permeation pathways.
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 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Monocellular and Multicellular Parasites Infesting Humans: A Review of Calcium Ion Mechanisms.Biomedicines · 2025Review
- Structural mechanisms of PIPeLife · 2025Article
- Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1.Nature communications · 2023Article
- Discovery and characterization of ORM-11372, a novel inhibitor of the sodium-calcium exchanger with positive inotropic activity.British journal of pharmacology · 2020Article
- Modulation of the cardiac NaCell calcium · 2020Review
- Key residues controlling bidirectional ion movements in NaCell calcium · 2018Article
- Molecular determinants of pH regulation in the cardiac NaThe Journal of general physiology · 2018Article
- The prokaryotic NaThe Journal of general physiology · 2018Article
- Phylogenetic analysis and protein structure modelling identifies distinct Ca(2+)/Cation antiporters and conservation of gene family structure within Arabidopsis and rice species.Rice (New York, N.Y.) · 2016Article
- Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger.Nature structural & molecular biology · 2016Article
- Asymmetric Preorganization of Inverted Pair Residues in the Sodium-Calcium Exchanger.Scientific reports · 2016Article
- Na+/Ca2+ exchange and Na+/K+-ATPase in the heart.The Journal of physiology · 2015Review
- Article
- Function and regulation of the Na+-Ca2+ exchanger NCX3 splice variants in brain and skeletal muscle.The Journal of biological chemistry · 2014Article
- Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions.Pflugers Archiv : European journal of physiology · 2014Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The Na(+)-Ca(2+) exchanger (NCX) is a ubiquitously expressed plasma membrane protein. It plays a fundamental role in Ca(2+) homeostasis by moving Ca(2+) out of the cell using the electrochemical gradient of Na(+) as the driving force. Recent structural studies of a homologous archaebacterial exchanger, NCX_Mj, revealed its outward configuration with two potential ion permeation pathways exposed to the extracellular environment. Based on the symmetry of NCX_Mj structure, an atomic model of an inward-facing conformation was generated showing similar pathways but directed to the cytoplasm. The presence of these water-filled cavities has yet to be confirmed experimentally, and it is unknown if the mammalian exchanger adopts the same structure. In this study, we mutated multiple residues within transmembrane segments 2 and 7 of NCX1.1 (cardiac isoform) to cysteines, allowing us to investigate their sensitivity to membrane-impermeable sulfhydryl reagents as exchanger current block. By trapping NCX1.1 in the inward-facing configuration, we have mapped two differently sized cytoplasmic aqueous cavities, the access of which is modified during exchange. This data reveals movements of the protein associated with ion transport. Electrophysiological characterization shows that the conserved residues within transmembrane segments 2 and 7, coordinating Na(+) and Ca(2+) ions in NCX_Mj, play a fundamental role in NCX1.1. Our results suggest a similar architecture between the mammalian and archaebacterial exchangers.
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