ArticleProceedings of the National Academy of Sciences of the United States of America2012
Genetic activation of BK currents in vivo generates bidirectional effects on neuronal excitability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Striatal neuron dysfunction in C9ORF72-FTD/ALS is driven by AIS and potassium channel dysregulation.Cell reports · 2026Article
- The NMDAR-BK channelosomes as regulators of synaptic plasticity.Biochemical Society transactions · 2025Review
- BK channels mediate a presynaptic form of mGluR-LTD in the neonatal hippocampus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural mapping of patient-associated KCNMA1 gene variants.Biophysical journal · 2024Article
- The BKPhysiological reports · 2024Article
- BK Channelopathies andAnnual review of physiology · 2024Review
- Large conductance voltage-and calcium-activated KFrontiers in pharmacology · 2024Review
- Disease-associated KCNMA1 variants decrease circadian clock robustness in channelopathy mouse models.The Journal of general physiology · 2023Article
- BK channels of five different subunit combinations underlie the de novo KCNMA1 G375R channelopathy.The Journal of general physiology · 2023Article
- CaInternational journal of molecular sciences · 2023Review
- Lysosomal Potassium Channels.Handbook of experimental pharmacology · 2023Review
- Further Studies on the Role of BTBD9 in the Cerebellum, Sleep-like Behaviors and the Restless Legs Syndrome.Neuroscience · 2022Article
- Article
- Inhibition of BKCell death discovery · 2022Article
- An emerging spectrum of variants and clinical features inChannels (Austin, Tex.) · 2021Review
- BK channel activation by L-type CaJournal of neurophysiology · 2021Article
- Mutations and Protein Interaction Landscape Reveal Key Cellular Events Perturbed in Upper Motor Neurons with HSP and PLS.Brain sciences · 2021Article
- BK Channel Regulation of Afterpotentials and Burst Firing in Cerebellar Purkinje Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Contributions of CaFrontiers in physiology · 2021Article
- Ion Channels Controlling Circadian Rhythms in Suprachiasmatic Nucleus Excitability.Physiological reviews · 2020Review
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Authors and funding
2 authors.
Funding
Abstract
Large-conductance calcium-activated potassium channels (BK) are potent negative regulators of excitability in neurons and muscle, and increasing BK current is a novel therapeutic strategy for neuro- and cardioprotection, disorders of smooth muscle hyperactivity, and several psychiatric diseases. However, in some neurons, enhanced BK current is linked with seizures and paradoxical increases in excitability, potentially complicating the clinical use of agonists. The mechanisms that switch BK influence from inhibitory to excitatory are not well defined. Here we investigate this dichotomy using a gain-of-function subunit (BK(R207Q)) to enhance BK currents. Heterologous expression of BK(R207Q) generated currents that activated at physiologically relevant voltages in lower intracellular Ca(2+), activated faster, and deactivated slower than wild-type currents. We then used BK(R207Q) expression to broadly augment endogenous BK currents in vivo, generating a transgenic mouse from a circadian clock-controlled Period1 gene fragment (Tg-BK(R207Q)). The specific impact on excitability was assessed in neurons of the suprachiasmatic nucleus (SCN) in the hypothalamus, a cell type where BK currents regulate spontaneous firing under distinct day and night conditions that are defined by different complements of ionic currents. In the SCN, Tg-BK(R207Q) expression converted the endogenous BK current to fast-activating, while maintaining similar current-voltage properties between day and night. Alteration of BK currents in Tg-BK(R207Q) SCN neurons increased firing at night but decreased firing during the day, demonstrating that BK currents generate bidirectional effects on neuronal firing under distinct conditions.
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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.