ArticleThe Journal of general physiology2009
Mechanism of increased BK channel activation from a channel mutation that causes epilepsy.
Article in The Journal of general physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- The Role of Photobiomodulation to Modulate Ion Channels in the Nervous System: A Systematic Review.Cellular and molecular neurobiology · 2024Pooled it
- Involvement of BK Channels and Ryanodine Receptors in Salicylate-induced Tinnitus.Molecular neurobiology · 2025Article
- Evaluation of fourChannels (Austin, Tex.) · 2024Article
- Activation mechanism and novel binding sites of the BKLife science alliance · 2024Article
- Structural mapping of patient-associated KCNMA1 gene variants.Biophysical journal · 2024Article
- Attenuating midline thalamus bursting to mitigate absence epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- BK Channelopathies andAnnual review of physiology · 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
- Striatal CDK5 Regulates Cholinergic Neuron Activation and Dyskinesia-like Behaviors through BK Channels.Research (Washington, D.C.) · 2023Article
- An allosteric modulator activates BK channels by perturbing coupling between CaNature communications · 2022Article
- Article
- Article
- Invertebrate neurons as a simple model to study the hyperexcitable state of epileptic disorders in single cells, monosynaptic connections, and polysynaptic circuits.Biophysical reviews · 2022Review
- Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- An emerging spectrum of variants and clinical features inChannels (Austin, Tex.) · 2021Review
- State-dependent inhibition of BK channels by the opioid agonist loperamide.The Journal of general physiology · 2021Article
- BK Channel Gating Mechanisms: Progresses Toward a Better Understanding of Variants Linked Neurological Diseases.Frontiers in physiology · 2021Review
- A Gain-of-Function Mutation in KCNMA1 Causes Dystonia Spells Controlled With Stimulant Therapy.Movement disorders : official journal of the Movement Disorder Society · 2020Article
- FeACS chemical biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Concerted depolarization and Ca(2+) rise during neuronal action potentials activate large-conductance Ca(2+)- and voltage-dependent K(+) (BK) channels, whose robust K(+) currents increase the rate of action potential repolarization. Gain-of-function BK channels in mouse knockout of the inhibitory beta 4 subunit and in a human mutation (alpha(D434G)) have been linked to epilepsy. Here, we investigate mechanisms underlying the gain-of-function effects of the equivalent mouse mutation (alpha(D369G)), its modulation by the beta 4 subunit, and potential consequences of the mutation on BK currents during action potentials. Kinetic analysis in the context of the Horrigan-Aldrich allosteric gating model revealed that changes in intrinsic and Ca(2+)-dependent gating largely account for the gain-of-function effects. D369G causes a greater than twofold increase in the closed-to-open equilibrium constant (6.6e(-7)-->1.65e(-6)) and an approximate twofold decrease in Ca(2+)-dissociation constants (closed channel: 11.3-->5.2 microM; open channel: 0.92-->0.54 microM). The beta 4 subunit inhibits mutant channels through a slowing of activation kinetics. In physiological recording solutions, we established the Ca(2+) dependence of current recruitment during action potential-shaped stimuli. D369G and beta 4 have opposing effects on BK current recruitment, where D369G reduces and beta 4 increases K(1/2) (K(1/2) microM: alpha(WT) 13.7, alpha(D369G) 6.3, alpha(WT)/beta 4 24.8, and alpha(D369G)/beta 4 15.0). Collectively, our results suggest that the D369G enhancement of intrinsic gating and Ca(2+) binding underlies greater contributions of BK current in the sharpening of action potentials for both alpha and alpha/beta 4 channels.
Indexed as
Identifiers
What OpenQuestion holds
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.