ArticleThe Journal of biological chemistry2009
Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 113 citations in OpenAlex.
- Potential therapeutic targeting of BKMolecular oncology · 2026Review
- Sodium disrupts mitochondrial energy metabolism to execute NECSO.Nature communications · 2025Article
- Sodium channels in non-excitable cells: powerful actions and therapeutic targets beyond Hodgkin and Huxley.Trends in cell biology · 2025Review
- Voltage-gated sodium channels in cancers.Biomarker research · 2024Review
- Therapeutic targeting of voltage-gated sodium channel NaFrontiers in pharmacology · 2024Review
- Review
- The Role οf Ion Channels in the Development and Progression of Prostate Cancer.Molecular diagnosis & therapy · 2023Review
- Voltage-gated sodium channels: from roles and mechanisms in the metastatic cell behavior to clinical potential as therapeutic targets.Frontiers in pharmacology · 2023Review
- Tumors derived from lung cancer cells respond differently to treatment with sodium valproate (a HDAC inhibitor) in a chicken embryo chorioallantoic membrane model.Histology and histopathology · 2022Article
- Article
- The voltage-gated KPlatelets · 2022Article
- The Role of Calcium Signaling in Melanoma.International journal of molecular sciences · 2022Review
- Wireless Localized Electrical Stimulation Generated by an Ultrasound-Driven Piezoelectric Discharge Regulates Proinflammatory Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers.iScience · 2021Review
- Structural and Functional Characterization of a NaCirculation research · 2021Article
- Influence of nNav1.5 on MHC class I expression in breast cancer.Journal of biosciences · 2021Article
- Alterations of Ion Homeostasis in Cancer Metastasis: Implications for Treatment.Frontiers in oncology · 2021Review
- Mice Heterozygous for the Sodium Channel Scn8a (Nav1.6) Have Reduced Inflammatory Responses During EAE and Following LPS Challenge.Frontiers in immunology · 2021Article
- Neosaxitoxin Inhibits the Expression of Inflammation Markers of the M1 Phenotype in Macrophages.Marine drugs · 2020Article
- Voltage gated sodium channels in cancer and their potential mechanisms of action.Channels (Austin, Tex.) · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Voltage-gated sodium channels initiate electrical signaling in excitable cells such as muscle and neurons. They also are expressed in non-excitable cells such as macrophages and neoplastic cells. Previously, in macrophages, we demonstrated expression of SCN8A, the gene that encodes the channel NaV1.6, and intracellular localization of NaV1.6 to regions near F-actin bundles, particularly at areas of cell attachment. Here we show that a splice variant of NaV1.6 regulates cellular invasion through its effects on podosome and invadopodia formation in macrophages and melanoma cells. cDNA sequence analysis of SCN8A from THP-1 cells, a human monocyte-macrophage cell line, confirmed the expression of a full-length splice variant that lacks exon 18. Immunoelectron microscopy demonstrated NaV1.6-positive staining within the electron dense podosome rosette structure. Pharmacologic antagonism with tetrodotoxin (TTX) in differentiated THP-1 cells or absence of functional NaV1.6 through a naturally occurring mutation (med) in mouse peritoneal macrophages inhibited podosome formation. Agonist-mediated activation of the channel with veratridine caused release of sodium from cationic vesicular compartments, uptake by mitochondria, and mitochondrial calcium release through the Na/Ca exchanger. Invasion by differentiated THP-1 and HTB-66 cells, an invasive melanoma cell line, through extracellular matrix was inhibited by TTX. THP-1 invasion also was inhibited by small hairpin RNA knockdown of SCN8A. These results demonstrate that a variant of NaV1.6 participates in the control of podosome and invadopodia formation and suggest that intracellular sodium release mediated by NaV1.6 may regulate cellular invasion of macrophages and melanoma cells.
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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.