ArticleJournal of neurophysiology2016
Knockout of the BK β4-subunit promotes a functional coupling of BK channels and ryanodine receptors that mediate a fAHP-induced increase in excitability.
Article in Journal of neurophysiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Smooth muscle of the lower urinary tract: BK-RyR coupling in physiology and pathophysiology.Journal of muscle research and cell motility · 2025Review
- Environmental Enrichment Suppresses Food Seeking and Increases Inhibitory Interneuron Excitability While Decreasing Corticothalamic Neuronal Recruitment in the Prelimbic Cortex.The European journal of neuroscience · 2025Article
- Food seeking suppression by environmental enrichment accompanies cell type- and circuit-specific prelimbic cortical modulation.bioRxiv : the preprint server for biology · 2025Article
- Neuronal autophagy controls excitability via ryanodine receptor-mediated regulation of calcium-activated potassium channel function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- BK Channelopathies andAnnual review of physiology · 2024Review
- Ethanol Metabolite, Acetate, Increases Excitability of the Central Nucleus of Amygdala Neurons through Activation of NMDA Receptors.ACS chemical neuroscience · 2023Article
- CaInternational journal of molecular sciences · 2023Review
- Further Studies on the Role of BTBD9 in the Cerebellum, Sleep-like Behaviors and the Restless Legs Syndrome.Neuroscience · 2022Article
- Article
- Ion Channel Partnerships: Odd and Not-So-Odd Couples Controlling Neuronal Ion Channel Function.International journal of molecular sciences · 2022Review
- BK channel activation by L-type CaJournal of neurophysiology · 2021Article
- Chronic ethanol exposure differentially alters neuronal function in the medial prefrontal cortex and dentate gyrus.Neuropharmacology · 2021Article
- Oligodendrocytes, BK channels and the preservation of myelin.F1000Research · 2021Review
- Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes.Frontiers in physiology · 2021Review
- BK Channels Are Activated by Functional Coupling With L-Type CaFrontiers in insect science · 2021Article
- Regulation of chemoconvulsant-induced seizures by store-operated Orai1 channels.The Journal of physiology · 2020Article
- Review
- Regulation of BK Channels by Beta and Gamma Subunits.Annual review of physiology · 2019Review
- Neuroadaptations in the dentate gyrus following contextual cued reinstatement of methamphetamine seeking.Brain structure & function · 2018Article
- A role for corticotropin-releasing factor signaling in the lateral habenula and its modulation by early-life stress.Science signaling · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
BK channels are large-conductance calcium- and voltage-activated potassium channels with diverse properties. Knockout of the accessory BK β4-subunit in hippocampus dentate gyrus granule neurons causes BK channels to change properties from slow-gated type II channels to fast-gated type I channels that sharpen the action potential, increase the fast afterhyperpolarization (fAHP) amplitude, and increase spike frequency. Here we studied the calcium channels that contribute to fast-gated BK channel activation and increased excitability of β4 knockout neurons. By using pharmacological blockers during current-clamp recording, we find that BK channel activation during the fAHP is dependent on ryanodine receptor activation. In contrast, L-type calcium channel blocker (nifedipine) affects the BK channel-dependent repolarization phase of the action potential but has no effect on the fAHP. Reducing BK channel activation during the repolarization phase with nifedipine, or during the fAHP with ryanodine, indicated that it is the BK-mediated increase of the fAHP that confers proexcitatory effects. The proexcitatory role of the fAHP was corroborated using dynamic current clamp. Increase or decrease of the fAHP amplitude during spiking revealed an inverse relationship between fAHP amplitude and interspike interval. Finally, we show that the seizure-prone ryanodine receptor gain-of-function (R2474S) knockin mice have an unaltered repolarization phase but larger fAHP and increased AP frequency compared with their control littermates. In summary, these results indicate that an important role of the β4-subunit is to reduce ryanodine receptor-BK channel functional coupling during the fAHP component of the action potential, thereby decreasing excitability of dentate gyrus neurons.
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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.