ArticleAmerican journal of physiology. Cell physiology2009
Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems.
Article in American journal of physiology. Cell physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 95 citations in OpenAlex.
- Bioinformatics analysis reveals shared molecular pathways for relationship between ulcerative colitis and primary sclerosing cholangitis.Genomics & informatics · 2025Article
- Cardiovascular effects and safety of classic psychedelics.Nature cardiovascular research · 2025Review
- The proarrhythmogenic role of autonomics and emerging neuromodulation approaches to prevent sudden death in cardiac ion channelopathies.Cardiovascular research · 2024Review
- 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
- Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems.Cellular and molecular neurobiology · 2022Review
- Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders.Neuroscience and biobehavioral reviews · 2022Review
- Sigma-1 receptor ligands improves ventricular repolarization-related ion remodeling in rats with major depression disorder.Psychopharmacology · 2021Article
- Sigmar1's Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology.Frontiers in physiology · 2021Review
- Haloperidol and sudden death in first acute myocardial infarction.International journal of cardiology. Heart & vasculature · 2020Article
- Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies? A systematic review.International journal of cardiology. Heart & vasculature · 2020Review
- The Molecular Function of σ Receptors: Past, Present, and Future.Trends in pharmacological sciences · 2019Review
- Allosteric Modulators of Sigma-1 Receptor: A Review.Frontiers in pharmacology · 2019Review
- The Sigma-1 Receptor: When Adaptive Regulation of Cell Electrical Activity Contributes to Stimulant Addiction and Cancer.Frontiers in neuroscience · 2019Review
- Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
- The Roles of Intracellular Chaperone Proteins, Sigma Receptors, in Parkinson's Disease (PD) and Major Depressive Disorder (MDD).Frontiers in pharmacology · 2019Review
- Molecular Interplay Between the Sigma-1 Receptor, Steroids, and Ion Channels.Frontiers in pharmacology · 2019Review
- Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process.Frontiers in pharmacology · 2018Article
- Sigma-1 receptor ligands inhibit catecholamine secretion from adrenal chromaffin cells due to block of nicotinic acetylcholine receptors.Journal of neurochemistry · 2017Article
- Sigma-1 Receptor Plays a Negative Modulation on N-type Calcium Channel.Frontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The sigma-receptor, a broadly distributed integral membrane protein with a novel structure, is known to modulate various voltage-gated K(+) and Ca(2+) channels through a mechanism that involves neither G proteins nor phosphorylation. The present study investigated the modulation of the heart voltage-gated Na(+) channel (Na(v)1.5) by sigma-receptors. The sigma(1)-receptor ligands [SKF-10047 and (+)-pentazocine] and sigma(1)/sigma(2)-receptor ligands (haloperidol and ditolylguanidine) all reversibly inhibited Na(v)1.5 channels to varying degrees in human embryonic kidney 293 (HEK-293) cells and COS-7 cells, but the sigma(1)-receptor ligands were less effective in COS-7 cells. The same four ligands also inhibited Na(+) current in neonatal mouse cardiac myocytes. In sigma(1)-receptor knockout myocytes, the sigma(1)-receptor-specific ligands were far less effective in modulating Na(+) current, but the sigma(1)/sigma(2)-receptor ligands modulated Na(+) channels as well as in wild type. Photolabeling with the sigma(1)-receptor photoprobe [(125)I]-iodoazidococaine demonstrated that sigma(1)-receptors were abundant in heart and HEK-293 cells, but scarce in COS-7 cells. This difference was consistent with the greater efficacy of sigma(1)-receptor-specific ligands in HEK-293 cells than in COS-7 cells. sigma-Receptors modulated Na(+) channels despite the omission of GTP and ATP from the patch pipette solution. sigma-Receptor-mediated inhibition of Na(+) current had little if any voltage dependence and produced no change in channel kinetics. Na(+) channels represent a new addition to the large number of voltage-gated ion channels modulated by sigma-receptors. The modulation of Na(v)1.5 channels by sigma-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity.
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