ArticleMolecular & cellular proteomics : MCP2008
Profiling the phospho-status of the BKCa channel alpha subunit in rat brain reveals unexpected patterns and complexity.
Article in Molecular & cellular proteomics : MCP, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 86 citations in OpenAlex.
- Tuning the gate and the gear: The LRRC26 (γ1) subunit modulates intrinsic gating and voltage-sensor coupling of the BK channel.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tuning the gate and the gear: The LRRC26 (bioRxiv : the preprint server for biology · 2025Article
- Structural mapping of patient-associated KCNMA1 gene variants.Biophysical journal · 2024Article
- BK Channelopathies andAnnual review of physiology · 2024Review
- Article
- CaInternational journal of molecular sciences · 2023Review
- Striatal CDK5 Regulates Cholinergic Neuron Activation and Dyskinesia-like Behaviors through BK Channels.Research (Washington, D.C.) · 2023Article
- Protein Kinase C-Mediated Phosphorylation and α2δ-1 Interdependently Regulate NMDA Receptor Trafficking and Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Conserved Role of the Large Conductance Calcium-Activated Potassium Channel, KCirculation. Genomic and precision medicine · 2021Article
- 14-3-3γ, a novel regulator of the large-conductance CaAmerican journal of physiology. Renal physiology · 2020Article
- Upregulation of Beta4 subunit of BKMolecular brain · 2020Article
- Voltage-gated calcium channel αF1000Research · 2018Review
- Large-conductance CaThe Journal of physiology · 2017Article
- The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection.The Biochemical journal · 2017Review
- Identification of Cav2-PKCβ and Cav2-NOS1 complexes as entities for ultrafast electrochemical coupling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- The unique N-terminal sequence of the BKCa channel α-subunit determines its modulation by β-subunits.PloS one · 2017Article
- An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron.American journal of physiology. Cell physiology · 2016Review
- Casein kinase-mediated phosphorylation of serine 839 is necessary for basolateral localization of the Ca²⁺-activated non-selective cation channel TRPM4.Pflugers Archiv : European journal of physiology · 2015Article
- MaxiK channel and cell signalling.Pflugers Archiv : European journal of physiology · 2014Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Molecular diversity of ion channel structure and function underlies variability in electrical signaling in nerve, muscle, and non-excitable cells. Protein phosphorylation and alternative splicing of pre-mRNA are two important mechanisms to generate structural and functional diversity of ion channels. However, systematic mass spectrometric analyses of in vivo phosphorylation and splice variants of ion channels in native tissues are largely lacking. Mammalian large-conductance calcium-activated potassium (BK(Ca)) channels are tetramers of alpha subunits (BKalpha) either alone or together with beta subunits, exhibit exceptionally large single channel conductance, and are dually activated by membrane depolarization and intracellular Ca(2+). The cytoplasmic C terminus of BKalpha is subjected to extensive pre-mRNA splicing and, as predicted by several algorithms, offers numerous phospho-acceptor amino acids. Here we use nanoflow liquid chromatography tandem mass spectrometry on BK(Ca) channels affinity-purified from rat brain to analyze in vivo BKalpha phosphorylation and splicing. We found 7 splice variations and identified as many as 30 Ser/Thr in vivo phosphorylation sites; most of which were not predicted by commonly used algorithms. Of the identified phosphosites 23 are located in the C terminus, four were found on splice insertions. Electrophysiological analyses of phospho- and dephosphomimetic mutants transiently expressed in HEK-293 cells suggest that phosphorylation of BKalpha differentially modulates the voltage- and Ca(2+)-dependence of channel activation. These results demonstrate that the pore-forming subunit of BK(Ca) channels is extensively phosphorylated in the mammalian brain providing a molecular basis for the regulation of firing pattern and excitability through dynamic modification of BKalpha structure and function.
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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.