ArticleThe Journal of general physiology2015
Transient receptor potential melastatin 3 is a phosphoinositide-dependent ion channel.
Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- TRPM3 mediates spontaneous pain and mechanical allodynia in a mouse model of chronic orofacial neuropathy.Cell reports. Medicine · 2026Article
- Muscarinic Receptor Antagonism and TRPM3 Activation as Stimulators of Mitochondrial Function and Axonal Repair in Diabetic Sensorimotor Polyneuropathy.International journal of molecular sciences · 2025Review
- Stimulus-Transcription Coupling of TRPM3 Channels: A Signaling Pathway from the Plasma Membrane to the Nucleus.Biomolecules · 2025Review
- TRPM3, TRPM4, and TRPM5 as thermo-sensitive channels.The journal of physiological sciences : JPS · 2024Review
- Signal Transduction of Transient Receptor Potential TRPM8 Channels: Role of PIP5K, Gq-Proteins, and c-Jun.Molecules (Basel, Switzerland) · 2024Article
- A Cataract-Causing Mutation in the TRPM3 Cation Channel Disrupts Calcium Dynamics in the Lens.Cells · 2024Article
- Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation.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
- TRP Channels as Molecular Targets to Relieve Endocrine-Related Diseases.Frontiers in molecular biosciences · 2022Review
- Bradykinin-Induced Sensitization of Transient Receptor Potential Channel Melastatin 3 Calcium Responses in Mouse Nociceptive Neurons.Frontiers in cellular neuroscience · 2022Article
- Control of TRPM3 Ion Channels by Protein Kinase CK2-Mediated Phosphorylation in Pancreatic β-Cells of the Line INS-1.International journal of molecular sciences · 2021Article
- The newest TRP channelopathy: Gain of function TRPM3 mutations cause epilepsy and intellectual disability.Channels (Austin, Tex.) · 2021Review
- Mutation of the TRPM3 cation channel underlies progressive cataract development and lens calcification associated with pro-fibrotic and immune cell responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Methods to study phosphoinositide regulation of ion channels.Methods in enzymology · 2021Article
- TRPM3 in Brain (Patho)Physiology.Frontiers in cell and developmental biology · 2021Review
- The TRPM3 ion channel mediates nociception but not itch evoked by endogenous pruritogenic mediators.Biochemical pharmacology · 2021Article
- Molecular dysregulation of ciliary polycystin-2 channels caused by variants in the TOP domain.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms.eLife · 2020Article
- Review
- TRPM3_miR-204: a complex locus for eye development and disease.Human genomics · 2020Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphoinositides are emerging as general regulators of the functionally diverse transient receptor potential (TRP) ion channel family. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been reported to positively regulate many TRP channels, but in several cases phosphoinositide regulation is controversial. TRP melastatin 3 (TRPM3) is a heat-activated ion channel that is also stimulated by chemical agonists, such as pregnenolone sulfate. Here, we used a wide array of approaches to determine the effects of phosphoinositides on TRPM3. We found that channel activity in excised inside-out patches decreased over time (rundown), an attribute of PI(4,5)P2-dependent ion channels. Channel activity could be restored by application of either synthetic dioctanoyl (diC8) or natural arachidonyl stearyl (AASt) PI(4,5)P2. The PI(4,5)P2 precursor phosphatidylinositol 4-phosphate (PI(4)P) was less effective at restoring channel activity. TRPM3 currents were also restored by MgATP, an effect which was inhibited by two different phosphatidylinositol 4-kinase inhibitors, or by pretreatment with a phosphatidylinositol-specific phospholipase C (PI-PLC) enzyme, indicating that MgATP acted by generating phosphoinositides. In intact cells, reduction of PI(4,5)P2 levels by chemically inducible phosphoinositide phosphatases or a voltage-sensitive 5'-phosphatase inhibited channel activity. Activation of PLC via muscarinic receptors also inhibited TRPM3 channel activity. Overall, our data indicate that TRPM3 is a phosphoinositide-dependent ion channel and that decreasing PI(4,5)P2 abundance limits its activity. As all other members of the TRPM family have also been shown to require PI(4,5)P2 for activity, our data establish PI(4,5)P2 as a general positive cofactor of this ion channel subfamily.
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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.