ArticleThe Journal of general physiology2005
Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current.
Article in The Journal of general physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
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Who cites it
168 citing papers in PubMed, 300 citations in OpenAlex.
- Small peptides derived from the autoinhibitory XY linker of phospholipase C-β isoforms inhibit enzyme activity and reduce inflammation.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- PIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Differential increase in endocannabinoid levels at the plasma and intracellular membranes.iScience · 2025Article
- Article
- Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.Science advances · 2024Article
- P2XBritish journal of pharmacology · 2024Article
- Calcium oscillations in HEK293 cells lacking SOCE suggest the existence of a balanced regulation of IPFrontiers in systems biology · 2024Article
- Contribution of TRPC3-mediated CaPflugers Archiv : European journal of physiology · 2023Article
- Involvement of CaCellular and molecular neurobiology · 2023Article
- Article
- Pharmacological potentiators of the calcium signaling cascade identified by high-throughput screening.PNAS nexus · 2023Article
- PLC regulates spontaneous glutamate release triggered by extracellular calcium and readily releasable pool size in neocortical neurons.Frontiers in cellular neuroscience · 2023Article
- Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells.The Journal of general physiology · 2022Article
- Hippocampal neurons maintain a large PtdIns(4)P pool that results in faster PtdIns(4,5)P2 synthesis.The Journal of general physiology · 2022Article
- Dishevelled coordinates phosphoinositide kinases PI4KIIIα and PIP5KIγ for efficient PtdInsP2 synthesis.Journal of cell science · 2022Article
- The Isoxazole Derivative of Usnic Acid Induces an ER Stress Response in Breast Cancer Cells That Leads to Paraptosis-like Cell Death.International journal of molecular sciences · 2022Article
- Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium.Biology · 2021Article
- Neuropeptide S Receptor Stimulation Excites Principal Neurons in Murine Basolateral Amygdala through a Calcium-Dependent Decrease in Membrane Potassium Conductance.Pharmaceuticals (Basel, Switzerland) · 2021Article
- β-arrestin-dependent PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2021Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
We have further tested the hypothesis that receptor-mediated modulation of KCNQ channels involves depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide-specific phospholipase C (PLC). We used four parallel assays to characterize the agonist-induced PLC response of cells (tsA or CHO cells) expressing M1 muscarinic receptors: translocation of two fluorescent probes for membrane lipids, release of calcium from intracellular stores, and chemical measurement of acidic lipids. Occupation of M1 receptors activates PLC and consumes cellular PIP2 in less than a minute and also partially depletes mono- and unphosphorylated phosphoinositides. KCNQ current is simultaneously suppressed. Two inhibitors of PLC, U73122 and edelfosine (ET-18-OCH3), can block the muscarinic actions completely, including suppression of KCNQ current. However, U73122 also had many side effects that were attributable to alkylation of various proteins. These were mimicked or occluded by prior reaction with the alkylating agent N-ethylmaleimide and included block of pertussis toxin-sensitive G proteins and effects that resembled a weak activation of PLC or an inhibition of lipid kinases. By our functional criteria, the putative PLC activator m-3M3FBS did stimulate PLC, but with a delay and an irregular time course. It also suppressed KCNQ current. The M1 receptor-mediated activation of PLC and suppression of KCNQ current were stopped by lowering intracellular calcium well below resting levels and were slowed by not allowing intracellular calcium to rise in response to PLC activation. Thus calcium release induced by PLC activation feeds back immediately on PLC, accelerating it during muscarinic stimulation in strong positive feedback. These experiments clarify important properties of receptor-coupled PLC responses and their inhibition in the context of the living cell. In each test, the suppression of KCNQ current closely paralleled the expected fall of PIP2. The results are described by a kinetic model.
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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.