ArticlePhysiological reports2019
The sigma-1 receptor behaves as an atypical auxiliary subunit to modulate the functional characteristics of Kv1.2 channels expressed in HEK293 cells.
Article in Physiological reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Competitive modulation of KFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Regulation of Kv1.2 Redox-Sensitive Gating by the Transmembrane Lectin LMAN2.Function (Oxford, England) · 2024Article
- Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development.Frontiers in pharmacology · 2022Review
- Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders.Neuroscience and biobehavioral reviews · 2022Review
- Emerging Benefits: Pathophysiological Functions and Target Drugs of the Sigma-1 Receptor in Neurodegenerative Diseases.Molecular neurobiology · 2021Review
- A NovelInternational journal of molecular sciences · 2021Article
- Regulation of KMembranes · 2021Article
- Article
- Sigma-1 receptor activation-induced glycolytic ATP production and endothelial barrier enhancement.Microcirculation (New York, N.Y. : 1994) · 2020Article
- An ion channel in the company of a transporter.The Journal of general physiology · 2020Article
- PB28, the Sigma-1 and Sigma-2 Receptors Modulator With Potent Anti-SARS-CoV-2 Activity: A Review About Its Pharmacological Properties and Structure Affinity Relationships.Frontiers in pharmacology · 2020Review
- The sigma-1 receptor behaves as an atypical auxiliary subunit to modulate the functional characteristics of Kv1.2 channels expressed in HEK293 cells.Physiological reports · 2019Article
- The Sigma-1 Receptor: When Adaptive Regulation of Cell Electrical Activity Contributes to Stimulant Addiction and Cancer.Frontiers in neuroscience · 2019Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of Kv1.2 within Kv1.x potassium channel complexes is critical in maintaining appropriate neuronal excitability and determining the threshold for action potential firing. This is attributed to the interaction of Kv1.2 with a hitherto unidentified protein that confers bimodal channel activation gating, allowing neurons to adapt to repetitive trains of stimulation and protecting against hyperexcitability. One potential protein candidate is the sigma-1 receptor (Sig-1R), which regulates other members of the Kv1.x channel family; however, the biophysical nature of the interaction between Sig-1R and Kv1.2 has not been elucidated. We hypothesized that Sig-1R may regulate Kv1.2 and may further act as the unidentified modulator of Kv1.2 activation. In transiently transfected HEK293 cells, we found that ligand activation of the Sig-1R modulates Kv1.2 current amplitude. More importantly, Sig-1R interacts with Kv1.2 in baseline conditions to influence bimodal activation gating. These effects are abolished in the presence of the auxiliary subunit Kvβ2 and when the Sig-1R mutation underlying ALS16 (Sig-1R-E102Q), is expressed. These data suggest that Kvβ2 occludes the interaction of Sig-1R with Kv1.2, and that E102 may be a residue critical for Sig-1R modulation of Kv1.2. The results of this investigation describe an important new role for Sig-1R in the regulation of neuronal excitability and introduce a novel mechanism of pathophysiology in Sig-1R dysfunction.
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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.