ArticleThe Journal of general physiology2010
Kinetics of PIP2 metabolism and KCNQ2/3 channel regulation studied with a voltage-sensitive phosphatase in living cells.
Article in The Journal of general physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
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Who cites it
148 citing papers in PubMed, 198 citations in OpenAlex.
- From lipid dynamics to precision predictions: A new approach methodology for precision modeling of phosphoinositide signaling.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- Dynamic cholinergic signaling differentially desynchronizes cortical microcircuits dependent on modulation rate and network connectivity.PLoS computational biology · 2026Article
- Distinct impact of PI(4)P flux on PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mas-Related G-Protein-Coupled Receptors: Emerging Roles in Neuropathic Pain.Biomolecules · 2026Review
- Endothelial Arf6 sustains capillary electrical signaling and cerebral blood flow through PIPbioRxiv : the preprint server for biology · 2025Article
- Computational Modeling of PI3K/AKT Pathway in Bipolar Disorder and Type 2 Diabetes: Implications for Lithium Treatment and Curcumin as a Potential Alternative.International journal of molecular sciences · 2025Article
- Constitutive opening of the Kv7.2 pore activation gate causesProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Atomistic mechanisms of the regulation of small-conductance CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Effect of hormone-induced plasma membrane phosphatidylinositol 4,5-bisphosphate depletion on receptor endocytosis suggests the importance of local regulation in phosphoinositide signaling.Scientific reports · 2024Article
- Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A.Nature communications · 2023Article
- Beyond analytic solution: Analysis of FRAP experiments by spatial simulation of the forward problem.Biophysical journal · 2023Article
- Contribution of TRPC3-mediated CaPflugers Archiv : European journal of physiology · 2023Article
- Role of K364 next to the active site cysteine in voltage-dependent phosphatase activity of Ci-VSP.Biophysical journal · 2023Article
- Acute phosphatidylinositol 4,5 bisphosphate depletion destabilizes sarcolemmal expression of cardiac L-type CaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dual regulation of Kv7.2/7.3 channels by long-chain n-alcohols.The Journal of general physiology · 2023Article
- Roles of Cholesterol and PtdIns(4,5)PAdvances in experimental medicine and biology · 2023Review
- Role of Lysosomal Cholesterol in Regulating PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Modulation of IJournal of cellular physiology · 2022Article
- Triclosan is a KCNQ3 potassium channel activator.Pflugers Archiv : European journal of physiology · 2022Article
- Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells.The Journal of general physiology · 2022Article
88 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
Funding
Abstract
The signaling phosphoinositide phosphatidylinositol 4,5-bisphosphate (PIP(2)) is synthesized in two steps from phosphatidylinositol by lipid kinases. It then interacts with KCNQ channels and with pleckstrin homology (PH) domains among many other physiological protein targets. We measured and developed a quantitative description of these metabolic and protein interaction steps by perturbing the PIP(2) pool with a voltage-sensitive phosphatase (VSP). VSP can remove the 5-phosphate of PIP(2) with a time constant of tau <300 ms and fully inhibits KCNQ currents in a similar time. PIP(2) was then resynthesized from phosphatidylinositol 4-phosphate (PIP) quickly, tau = 11 s. In contrast, resynthesis of PIP(2) after activation of phospholipase C by muscarinic receptors took approximately 130 s. These kinetic experiments showed that (1) PIP(2) activation of KCNQ channels obeys a cooperative square law, (2) the PIP(2) residence time on channels is <10 ms and the exchange time on PH domains is similarly fast, and (3) the step synthesizing PIP(2) by PIP 5-kinase is fast and limited primarily by a step(s) that replenishes the pool of plasma membrane PI(4)P. We extend the kinetic model for signaling from M(1) muscarinic receptors, presented in our companion paper in this issue (Falkenburger et al. 2010. J. Gen. Physiol. doi:10.1085/jgp.200910344), with this new information on PIP(2) synthesis and KCNQ interaction.
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