ArticleThe Journal of physiology2011
Decrease in phosphatidylinositol 4,5-bisphosphate levels mediates desensitization of the cold sensor TRPM8 channels.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 86 citations in OpenAlex.
- Transcriptome sequencing reveals Vmplc1 involved in regulating the pathogenicity of Valsa Mali under low temperature induction.BMC genomics · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8.Science advances · 2024Article
- Signal Transduction of Transient Receptor Potential TRPM8 Channels: Role of PIP5K, Gq-Proteins, and c-Jun.Molecules (Basel, Switzerland) · 2024Article
- Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets.PloS one · 2024Article
- Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets.bioRxiv : the preprint server for biology · 2023Article
- Progress in the Structural Basis of thermoTRP Channel Polymodal Gating.International journal of molecular sciences · 2023Review
- Expression of the C-Terminal Domain of Phospholipase Cβ3 Inhibits Signaling via Gαq-Coupled Receptors and Transient Receptor Potential Channels.International journal of molecular sciences · 2022Article
- On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications.Frontiers in oncology · 2022Review
- The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- Constitutive Phosphorylation as a Key Regulator of TRPM8 Channel Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel.Life (Basel, Switzerland) · 2021Review
- Methods to study phosphoinositide regulation of ion channels.Methods in enzymology · 2021Article
- Regulation of the cold-sensing TRPM8 channels by phosphoinositides and GChannels (Austin, Tex.) · 2020Review
- The cool things to know about TRPM8!Channels (Austin, Tex.) · 2020Review
- Current View of Ligand and Lipid Recognition by the Menthol Receptor TRPM8.Trends in biochemical sciences · 2020Review
- Negative Modulation of TRPM8 Channel Function by Protein Kinase C in Trigeminal Cold Thermoreceptor Neurons.International journal of molecular sciences · 2020Article
- Gi-coupled receptor activation potentiates Piezo2 currents via Gβγ.EMBO reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The activity of the cold- and menthol-activated transient receptor potential melastatin 8 (TRPM8) channels diminishes over time in the presence of extracellular Ca(2+), a phenomenon referred to as desensitization or adaptation. Here we show that activation of TRPM8 by cold or menthol evokes a decrease in cellular phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] levels. The decrease in PtdIns(4,5)P(2) levels was accompanied by increased inositol 1,4,5 trisphosphate (InsP(3)) production, and was inhibited by loading the cells with the Ca(2+) chelator BAPTA-AM, showing that it was the consequence of the activation of phospholipase C (PLC) by increased intracellular Ca(2+) concentrations. PtdIns(4,5)P(2) hydrolysis showed excellent temporal correlation with current desensitization in simultaneous patch clamp and fluorescence-based PtdIns(4,5)P(2) level measurements. Intracellular dialysis of PtdIns(4,5)P(2) inhibited desensitization both in native neuronal and recombinant TRPM8 channels. PtdIns(4)P, the precursor of PtdIns(4,5)P(2), did not inhibit desensitization, consistent with its minimal effect in excised patches. Omission of MgATP from the intracellular solution accelerated desensitization, and MgATP reactivated TRPM8 channels in excised patches in a phosphatidylinositol 4-kinase (PI4K)-dependent manner. PLC-independent depletion of PtdIns(4,5)P(2) using a voltage-sensitive phosphatase (ci-VSP) inhibited TRPM8 currents, and omission of ATP from the intracellular solution inhibited recovery from this inhibition. Inhibitors of PKC had no effect on the kinetics of desensitization. We conclude that Ca(2+) influx through TRPM8 activates a Ca(2+)-sensitive PLC isoform, and the resulting depletion of PtdIns(4,5)P(2) plays a major role in desensitization of both cold and menthol responses.
Indexed as
Identifiers
What OpenQuestion holds
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.