ArticleProceedings of the National Academy of Sciences of the United States of America2005
Low mobility of phosphatidylinositol 4,5-bisphosphate underlies receptor specificity of Gq-mediated ion channel regulation in atrial myocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 80 citations in OpenAlex.
- Molecular insights into profilin 1-dependent regulation of cellular phosphatidylinositol (4,5)-bisphosphate.Journal of cell science · 2026Article
- PKC isoform-specific targeting of the phosphorylation site SerinePflugers Archiv : European journal of physiology · 2026Article
- Higher-order transient structures and the principle of dynamic connectivity in membrane signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Angiotensin receptors and αPflugers Archiv : European journal of physiology · 2024Article
- Direct modulation of TRPC ion channels by Gα proteins.Frontiers in physiology · 2024Review
- Structure and Lateral Organization of Phosphatidylinositol 4,5-bisphosphate.Molecules (Basel, Switzerland) · 2020Review
- PIPProceedings of the National Academy of Sciences of the United States of America · 2020Review
- Teamwork: Ion channels and transporters join forces in the brain.Neuropharmacology · 2019Review
- PIPeLife · 2018Article
- Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIPProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis.The Journal of general physiology · 2018Review
- Chansporter complexes in cell signaling.FEBS letters · 2017Review
- SMIT1 Modifies KCNQ Channel Function and Pharmacology by Physical Interaction with the Pore.Biophysical journal · 2017Article
- KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Receptor Species-dependent Desensitization Controls KCNQ1/KCNE1 K+ Channels as Downstream Effectors of Gq Protein-coupled Receptors.The Journal of biological chemistry · 2016Article
- Membrane coordination of receptors and channels mediating the inhibition of neuronal ion currents by ADP.Purinergic signalling · 2016Article
- Does PKC activation increase the homologous desensitization of μ opioid receptors?British journal of pharmacology · 2015Article
- Counterion-mediated cluster formation by polyphosphoinositides.Chemistry and physics of lipids · 2014Review
- Article
- Membrane-sculpting BAR domains generate stable lipid microdomains.Cell reports · 2013Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have shown previously that cardiac G protein-gated inwardly rectifying K+ (GIRK) channels are inhibited by Gq protein-coupled receptors (GqPCRs) via phosphatidylinositol 4,5-bisphosphate (PIP2) depletion in a receptor-specific manner. To investigate the mechanism of receptor specificity, we examined whether the activation of GqPCRs induces localized PIP2 depletion. When we applied endothelin-1 to the bath, GIRK channel activities recorded in cell-attached patches were not changed, implying that PIP2 signal is not diffusible but is a localized signal. To test this possibility, we directly measured lateral diffusion by introducing fluorescence-labeled phosphoinositides to a small area of the membrane with patch pipettes. After pipettes were attached, phosphatidylinositol 4-monophosphate or phosphatidylinositol diffused rapidly to the entire membrane, whereas PIP2 was confined to the membrane patch inside the pipette. The confinement of PIP2 was disrupted after cytochalasin D treatment, suggesting that the cytoskeleton is responsible for the low mobility of PIP2. The diffusion coefficient (D) of PIP2 in the plasma membrane measured with the fluorescence recovery after photobleaching technique was 0.00039 microm2/s (n = 6), which is markedly lower than D of phosphatidylinositol (5.8 microm2/s, n = 5). Simulation of PIP2 concentration profiles by the diffusion model confirms that when D is small, the kinetics of PIP2 depletion at different distances from phospholipase C becomes similar to the characteristic kinetics of GIRK inhibition by different agonists. These results imply that PIP2 depletion is localized adjacent to GqPCRs because of its low mobility, and that spatial proximity of GqPCR and the target protein underlies the receptor specificity of PIP2-mediated signaling.
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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.