ArticleBritish journal of pharmacology2015
Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- SLO3: A Conserved Regulator of Sperm Membrane Potential.International journal of molecular sciences · 2023Review
- SLO3 in the fast lane: The latest male contraceptive target with a promising small-molecule inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Genetic deletion of the Tas2r143/Tas2r135/Tas2r126 cluster reveals that TAS2Rs may not mediate bitter tastant-induced bronchodilation.Journal of cellular physiology · 2021Article
- Review
- Cloning and characterization of the rat Slo3 (KBritish journal of pharmacology · 2020Article
- Structure-Based Identification and Characterization of Inhibitors of the Epilepsy-Associated KiScience · 2020Article
- Onion peel extract and its constituent, quercetin inhibits human Slo3 in a pH and calcium dependent manner.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Article
- A Novel Calcium-Activated Potassium Channel Controls Membrane Potential and Intracellular pH inFrontiers in cellular and infection microbiology · 2019Article
- International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.Pharmacological reviews · 2017Review
- An Exploration of Charge Compensating Ion Channels across the Phagocytic Vacuole of Neutrophils.Frontiers in pharmacology · 2017Article
- Emerging concepts in male contraception: a narrative review of novel, hormonal and non-hormonal options.Therapeutic advances in reproductive healthReview
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeThe Slo3 (KCa 5.1) channel is a major component of mammalian KSper (sperm potassium conductance) channels and inhibition of these channels by quinine and barium alters sperm motility. The aim of this investigation was to determine the mechanism by which these drugs inhibit Slo3 channels. EXPERIMENTAL APPROACH: Mouse (m) Slo3 (KCa 5.1) channels or mutant forms were expressed in Xenopus oocytes and currents recorded with 2-electrode voltage-clamp. Gain-of-function mSlo3 mutations were used to explore the state-dependence of the inhibition. The interaction between quinidine and mSlo3 channels was modelled by in silico docking. KEY
resultsSeveral drugs known to block KSper also affected mSlo3 channels with similar levels of inhibition. The inhibition induced by extracellular barium was prevented by increasing the extracellular potassium concentration. R196Q and F304Y mutations in the mSlo3 voltage sensor and pore, respectively, both increased channel activity. The F304Y mutation did not alter the effects of barium, but increased the potency of inhibition by both quinine and quinidine approximately 10-fold; this effect was not observed with the R196Q mutation. CONCLUSIONS AND IMPLICATIONS: Block of mSlo3 channels by quinine, quinidine and barium is not state-dependent. Barium inhibits mSlo3 outside the cell by interacting with the selectivity filter, whereas quinine and quinidine act from the inside, by binding in a hydrophobic pocket formed by the S6 segment of each subunit. Furthermore, we propose that the Slo3 channel activation gate lies deep within the pore between F304 in the S6 segment and the selectivity filter.
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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.