ArticleThe Journal of biological chemistry2012
The sigma-1 receptor binds to the Nav1.5 voltage-gated Na+ channel with 4-fold symmetry.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- Sigma receptor ligands in selected affective disorders, psychoses, and addictions - a narrative review.Pharmacological reports : PR · 2026Review
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- Effects of NaCell biochemistry and biophysics · 2025Review
- Mutated sigma-1R disrupts cell homeostasis in dHMN patient cells.Cellular and molecular life sciences : CMLS · 2025Article
- Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons.Biomolecules · 2025Article
- Article
- Sigma-1 receptor and seizures.Pharmacological research · 2023Review
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- Potassium and Calcium Channel Complexes as Novel Targets for Cancer Research.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Antagonism of Sigma-1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice.Alcoholism, clinical and experimental research · 2021Article
- Review
- Sigmar1's Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology.Frontiers in physiology · 2021Review
- Supramolecular clustering of the cardiac sodium channel Nav1.5 in HEK293F cells, with and without the auxiliary β3-subunit.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- The Functional Role of Voltage-Gated Sodium Channel Nav1.5 in Metastatic Breast Cancer.Frontiers in pharmacology · 2020Review
- Gating control of the cardiac sodium channel Nav1.5 by its β3-subunit involves distinct roles for a transmembrane glutamic acid and the extracellular domain.The Journal of biological chemistry · 2019Article
- Partners in Crime: Towards New Ways of Targeting Calcium Channels.International journal of molecular sciences · 2019Review
- Effect of Sigma-1 Receptors on Voltage-Gated Sodium Ion Channels in Colon Cancer Cell Line SW620.Bioelectricity · 2019Article
- The Molecular Function of σ Receptors: Past, Present, and Future.Trends in pharmacological sciences · 2019Review
- The Sigma-1 Receptor: When Adaptive Regulation of Cell Electrical Activity Contributes to Stimulant Addiction and Cancer.Frontiers in neuroscience · 2019Review
- Molecular Interplay Between the Sigma-1 Receptor, Steroids, and Ion Channels.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The sigma-1 receptor (Sig1R) is up-regulated in many human tumors and plays a role in the control of cancer cell proliferation and invasiveness. At the molecular level, the Sig1R modulates the activity of various ion channels, apparently through a direct interaction. We have previously shown using atomic force microscopy imaging that the Sig1R binds to the trimeric acid-sensing ion channel 1A with 3-fold symmetry. Here, we investigated the interaction between the Sig1R and the Nav1.5 voltage-gated Na(+) channel, which has also been implicated in promoting the invasiveness of cancer cells. We show that the Sig1R and Nav1.5 can be co-isolated from co-transfected cells, consistent with an intimate association between the two proteins. Atomic force microscopy imaging of the co-isolated proteins revealed complexes in which Nav1.5 was decorated by Sig1Rs. Frequency distributions of angles between pairs of bound Sig1Rs had two peaks, at ∼90° and ∼180°, and the 90° peak was about twice the size of the 180° peak. These results demonstrate that the Sig1R binds to Nav1.5 with 4-fold symmetry. Hence, each set of six transmembrane regions in Nav1.5 likely constitutes a Sig1R binding site, suggesting that the Sig1R interacts with the transmembrane regions of its partners. Interestingly, two known Sig1R ligands, haloperidol and (+)-pentazocine, disrupted the Nav1.5/Sig1R interaction both in vitro and in living cells. Finally, we show that endogenously expressed Sig1R and Nav1.5 also functionally interact.
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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.