ArticleThe Journal of biological chemistry2014
Structural determinants of phosphatidylinositol 4,5-bisphosphate (PIP2) regulation of BK channel activity through the RCK1 Ca2+ coordination site.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Pharmacological Relevance of β-, γ-, and LINGO Auxiliary Subunits in BK Channel Modulation.ChemMedChem · 2026Review
- Cholesterol, PtdIns(4,5)PbioRxiv : the preprint server for biology · 2026Article
- Discovery of non-opioid peptides that selectively relieve mechanical pain in rodents through inhibition of TRPV4 channels.Acta pharmacologica Sinica · 2026Article
- Lipid-mediated hydrophobic gating in the BK potassium channel.Nature communications · 2025Article
- A synthetic peptide, derived from neurotoxin GsMTx4, acts as a non-opioid analgesic to alleviate mechanical and neuropathic pain through the TRPV4 channel.Acta pharmaceutica Sinica. B · 2025Article
- Review
- Structural mapping of patient-associated KCNMA1 gene variants.Biophysical journal · 2024Article
- Subunit-specific inhibition of BK channels by piperine.Biophysical journal · 2024Article
- Membranes are functionalized by a proteolipid code.BMC biology · 2024Article
- Incorporating physics to overcome data scarcity in predictive modeling of protein function: A case study of BK channels.PLoS computational biology · 2023Article
- Incorporating physics to overcome data scarcity in predictive modeling of protein function: a case study of BK channels.bioRxiv : the preprint server for biology · 2023Article
- Cholesterol and PIPAdvances in experimental medicine and biology · 2023Article
- Specificities of Protein Homology Modeling for Allosteric Drug Design.Methods in molecular biology (Clifton, N.J.) · 2023Article
- External Hemin as an Inhibitor of Mitochondrial Large-Conductance Calcium-Activated Potassium Channel Activity.International journal of molecular sciences · 2022Article
- PKC regulation of ion channels: The involvement of PIPThe Journal of biological chemistry · 2022Review
- Spotlight on the Binding Affinity of Ion Channels for Phosphoinositides: From the Study of Sperm Flagellum.Frontiers in physiology · 2022Review
- An emerging spectrum of variants and clinical features inChannels (Austin, Tex.) · 2021Review
- From Bench to Biomolecular Simulation: Phospholipid Modulation of Potassium Channels.Journal of molecular biology · 2021Review
- The Large-Conductance, Calcium-Activated Potassium Channel: A Big Key Regulator of Cell Physiology.Frontiers in physiology · 2021Review
- Status Dystonicus, Oculogyric Crisis and Paroxysmal Dyskinesia in a 25 Year-Old Woman with a NovelTremor and other hyperkinetic movements (New York, N.Y.) · 2020Article
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5 authors.
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Abstract
Big or high conductance potassium (BK) channels are activated by voltage and intracellular calcium (Ca(2+)). Phosphatidylinositol 4,5-bisphosphate (PIP2), a ubiquitous modulator of ion channel activity, has been reported to enhance Ca(2+)-driven gating of BK channels, but a molecular understanding of this interplay or even of the PIP2 regulation of this channel's activity remains elusive. Here, we identify structural determinants in the KDRDD loop (which follows the αA helix in the RCK1 domain) to be responsible for the coupling between Ca(2+) and PIP2 in regulating BK channel activity. In the absence of Ca(2+), RCK1 structural elements limit channel activation through a decrease in the channel's PIP2 apparent affinity. This inhibitory influence of BK channel activation can be relieved by mutation of residues that (a) connect either the RCK1 Ca(2+) coordination site (Asp(367) or its flanking basic residues in the KDRDD loop) to the PIP2-interacting residues (Lys(392) and Arg(393)) found in the αB helix or (b) are involved in hydrophobic interactions between the αA and αB helix of the RCK1 domain. In the presence of Ca(2+), the RCK1-inhibitory influence of channel-PIP2 interactions and channel activity is relieved by Ca(2+) engaging Asp(367). Our results demonstrate that, along with Ca(2+) and voltage, PIP2 is a third factor critical to the integral control of BK channel activity.
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