ArticleThe Journal of general physiology2009
Fluorescence changes reveal kinetic steps of muscarinic receptor-mediated modulation of phosphoinositides and Kv7.2/7.3 K+ channels.
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 66 papers.
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Who cites it
66 citing papers in PubMed, 110 citations in OpenAlex.
- Population Pharmacokinetic and Exposure-Response Analysis of the Cognitive Effects of TAK-071 in Participants With Parkinson Disease and Cognitive Impairment.Clinical pharmacology in drug development · 2025Trial
- Phosphatidylserine and RhoB connect PI4P and PA metabolism to maintain plasma membrane identity.The Journal of cell biology · 2026Article
- Phosphatidylserine and RhoB connect phosphatidylinositol 4-phosphate and phosphatidic acid metabolism at the plasma membrane.bioRxiv : the preprint server for biology · 2025Article
- An integrated mechanism of GProceedings of the National Academy of Sciences of the United States of America · 2025Article
- TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia.The EMBO journal · 2024Article
- 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
- Two-step structural changes in M3 muscarinic receptor activation rely on the coupled GNature communications · 2023Article
- Conformational GPCR BRET Sensors Based on Bioorthogonal Labeling of Noncanonical Amino Acids.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Investigating G-protein coupled receptor signalling with light-emitting biosensors.Frontiers in physiology · 2023Review
- Examination of Intracellular GPCR-Mediated Signaling with High Temporal Resolution.International journal of molecular sciences · 2022Article
- Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells.The Journal of general physiology · 2022Article
- Letting the little light of mind shine: Advances and future directions in neurochemical detection.Neuroscience research · 2022Review
- Hippocampal neurons maintain a large PtdIns(4)P pool that results in faster PtdIns(4,5)P2 synthesis.The Journal of general physiology · 2022Article
- PIPCommunications biology · 2022Article
- Neurophotonic tools for microscopic measurements and manipulation: status report.Neurophotonics · 2022Article
- Frizzled BRET sensors based on bioorthogonal labeling of unnatural amino acids reveal WNT-induced dynamics of the cysteine-rich domain.Science advances · 2021Article
- Ethanol inhibits Kv7.2/7.3 channel open probability by reducing the PI(4,5)P2 sensitivity of Kv7.2 subunit.BMB reports · 2021Article
- Application of FRET Biosensors in Mechanobiology and Mechanopharmacological Screening.Frontiers in bioengineering and biotechnology · 2020Review
- With PIPs, you get ZIPs and blips.The Journal of general physiology · 2019Article
- Optical approaches for single-cell and subcellular analysis of GPCR-G protein signaling.Analytical and bioanalytical chemistry · 2019Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
G protein-coupled receptors initiate signaling cascades. M(1) muscarinic receptor (M(1)R) activation couples through Galpha(q) to stimulate phospholipase C (PLC), which cleaves phosphatidylinositol 4,5-bisphosphate (PIP(2)). Depletion of PIP(2) closes PIP(2)-requiring Kv7.2/7.3 potassium channels (M current), thereby increasing neuronal excitability. This modulation of M current is relatively slow (6.4 s to reach within 1/e of the steady-state value). To identify the rate-limiting steps, we investigated the kinetics of each step using pairwise optical interactions likely to represent fluorescence resonance energy transfer for M(1)R activation, M(1)R/Gbeta interaction, Galpha(q)/Gbeta separation, Galpha(q)/PLC interaction, and PIP(2) hydrolysis. Electrophysiology was used to monitor channel closure. Time constants for M(1)R activation (<100 ms) and M(1)R/Gbeta interaction (200 ms) are both fast, suggesting that neither of them is rate limiting during muscarinic suppression of M current. Galpha(q)/Gbeta separation and Galpha(q)/PLC interaction have intermediate 1/e times (2.9 and 1.7 s, respectively), and PIP(2) hydrolysis (6.7 s) occurs on the timescale of M current suppression. Overexpression of PLC accelerates the rate of M current suppression threefold (to 2.0 s) to become nearly contemporaneous with Galpha(q)/PLC interaction. Evidently, channel release of PIP(2) and closure are rapid, and the availability of active PLC limits the rate of M current suppression.
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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.