ArticleRespiratory research2010
Reverse mode Na+/Ca2+ exchange mediated by STIM1 contributes to Ca2+ influx in airway smooth muscle following agonist stimulation.
Article in Respiratory research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Urinary sodium, table salt use and incidence of late-onset asthma in females and males: evidence from a large prospective cohort.ERJ open research · 2026Article
- CaPhysiological reviews · 2024Review
- Molecular Modification of Transient Receptor Potential Canonical 6 Channels Modulates Calcium Dyshomeostasis in a Mouse Model Relevant to Malignant Hyperthermia.Anesthesiology · 2021Article
- Elucidation of Cellular Mechanisms That Regulate the Sustained Contraction and Relaxation of the Mammalian Iris.Investigative ophthalmology & visual science · 2020Article
- Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis.Science advances · 2020Article
- TRPV4 Complexes With the NaFrontiers in physiology · 2019Article
- Reverse mode of sodium/calcium exchanger subtype 1 contributes to detrusor overactivity in rats with partial bladder outflow obstruction.American journal of translational research · 2018Article
- NaFrontiers in pharmacology · 2018Article
- Cellular Na+ handling mechanisms involved in airway smooth muscle contraction (Review).International journal of molecular medicine · 2017Review
- Store-operated calcium entry is required for sustained contraction and CaThe Journal of physiology · 2017Article
- Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- STIM1-dependent Ca(2+) microdomains are required for myofilament remodeling and signaling in the heart.Scientific reports · 2016Article
- Relaxant effects of a hydroalcoholic extract of Ruta graveolens on isolated rat tracheal rings.Biological research · 2015Article
- Store-operated calcium entry and the localization of STIM1 and Orai1 proteins in isolated mouse sinoatrial node cells.Frontiers in physiology · 2015Article
- Clonally expanded human airway smooth muscle cells exhibit morphological and functional heterogeneity.Respiratory research · 2014Article
- Altered vascular smooth muscle function in the ApoE knockout mouse during the progression of atherosclerosis.Atherosclerosis · 2014Article
- Airway smooth muscle in airway reactivity and remodeling: what have we learned?American journal of physiology. Lung cellular and molecular physiology · 2013Review
- Activation of the endoplasmic reticulum calcium sensor STIM1 and store-operated calcium entry by rotavirus requires NSP4 viroporin activity.Journal of virology · 2013Article
- Multifaceted roles of STIM proteins.Pflugers Archiv : European journal of physiology · 2013Review
- Epigenetic alterations by DNA methylation in house dust mite-induced airway hyperresponsiveness.American journal of respiratory cell and molecular biology · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAgonist stimulation of airway smooth muscle (ASM) results in IP3 mediated Ca2+ release from the sarcoplasmic reticulum followed by the activation of store operated and receptor operated non-selective cation channels. Activation of these non-selective channels also results in a Na+ influx. This localised increase in Na+ levels can potentially switch the Na+/Ca2+ exchanger into reverse mode and so result in a further influx of Ca2+. The aim of this study was to characterise the expression and physiological function of the Na+/Ca2+ exchanger in cultured human bronchial smooth muscle cells and determine its contribution to agonist induced Ca2+ influx into these cells.
methodsThe expression profile of NCX (which encodes the Na+/Ca2+ exchanger) homologues in cultured human bronchial smooth muscle cells was determined by reverse transcriptase PCR. The functional activity of reverse mode NCX was investigated using a combination of whole cell patch clamp, intracellular Ca2+ measurements and porcine airway contractile analyses. KB-R7943 (an antagonist for reverse mode NCX) and target specific siRNA were utilised as tools to inhibit NCX function.
resultsNCX1 protein was detected in cultured human bronchial smooth muscle cells (HBSMC) cells and NCX1.3 was the only mRNA transcript variant detected. A combination of intracellular Na+ loading and addition of extracellular Ca2+ induced an outwardly rectifying current which was augmented following stimulation with histamine. This outwardly rectifying current was inhibited by 10 μM KB-R7943 (an antagonist of reverse mode NCX1) and was reduced in cells incubated with siRNA against NCX1. Interestingly, this outwardly rectifying current was also inhibited following knockdown of STIM1, suggesting for the first time a link between store operated cation entry and NCX1 activation. In addition, 10 μM KB-R7943 inhibited agonist induced changes in cytosolic Ca2+ and induced relaxation of porcine peripheral airways.
conclusionsTaken together, these data demonstrate a potentially important role for NCX1 in control of Ca2+ homeostasis and link store depletion via STIM1 directly with NCX activation.
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