ArticleProceedings of the National Academy of Sciences of the United States of America2005
A cysteine-rich motif confers hypoxia sensitivity to mammalian large conductance voltage- and Ca-activated K (BK) channel alpha-subunits.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. 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.
- Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial.Anesthesiology · 2024Trial
- Targeting the Carotid Body Function With Big-KPharmacology research & perspectives · 2026Article
- Cytochrome C-like Domain Within the Human BK Channel.International journal of molecular sciences · 2025Article
- Article
- Catsnap: a user-friendly algorithm for determining the conservation of protein variants reveals extensive parallelisms in the evolution of alternative splicing.The New phytologist · 2023Article
- The Use of Caffeine Citrate for Respiratory Stimulation in Acquired Central Hypoventilation Syndrome: A Case Series.Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures) · 2023Article
- The Large-Conductance, Calcium-Activated Potassium Channel: A Big Key Regulator of Cell Physiology.Frontiers in physiology · 2021Review
- History of Respiratory Stimulants.Journal of pain research · 2021Review
- Regulation of Ion Channel Function by Gas Molecules.Advances in experimental medicine and biology · 2021Review
- Hypoxic Regulation of the Large-Conductance, Calcium and Voltage-Activated Potassium Channel, BK.Frontiers in physiology · 2021Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Calcium- and voltage-gated BK channels in vascular smooth muscle.Pflugers Archiv : European journal of physiology · 2018Review
- The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection.The Biochemical journal · 2017Review
- BK channels in rat and human pulmonary smooth muscle cells are BKα-βPulmonary circulation · 2016Article
- BK Channels in the Central Nervous System.International review of neurobiology · 2016Review
- Alternatively Spliced Isoforms of KV10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes.The Journal of biological chemistry · 2015Article
- Oxidative modulation of voltage-gated potassium channels.Antioxidants & redox signaling · 2014Review
- S-acylation dependent post-translational cross-talk regulates large conductance calcium- and voltage- activated potassium (BK) channels.Frontiers in physiology · 2014Review
- The role of ion channels in the hypoxia-induced aggressiveness of glioblastoma.Frontiers in cellular neuroscience · 2014Article
- Opioid-induced respiratory depression: reversal by non-opioid drugs.F1000prime reports · 2014Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Cellular responses to hypoxia are tissue-specific and dynamic. However, the mechanisms that underlie this differential sensitivity to hypoxia are unknown. Large conductance voltage- and Ca-activated K (BK) channels are important mediators of hypoxia responses in many systems. Although BK channels are ubiquitously expressed, alternative pre-mRNA splicing of the single gene encoding their pore-forming alpha-subunits provides a powerful mechanism for generating functional diversity. Here, we demonstrate that the hypoxia sensitivity of BK channel alpha-subunits is splice-variant-specific. Sensitivity to hypoxia is conferred by a highly conserved motif within an alternatively spliced cysteine-rich insert, the stress-regulated exon (STREX), within the intracellular C terminus of the channel. Hypoxic inhibition of the STREX variant is Ca-sensitive and reversible, and it rapidly follows the change in oxygen tension by means of a mechanism that is independent of redox or CO regulation. Hypoxia sensitivity was abolished by mutation of the serine (S24) residue within the STREX insert. Because STREX splice-variant expression is tissue-specific and dynamically controlled, alternative splicing of BK channels provides a mechanism to control the plasticity of cellular responses to hypoxia.
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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.