ArticleThe Journal of general physiology1999
Synergistic activation of G protein-gated inwardly rectifying potassium channels by the betagamma subunits of G proteins and Na(+) and Mg(2+) ions.
Article in The Journal of general physiology, 1999. 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.
- A nonhydrolyzable candesartan cilexetil analog reveals synergistic activation as a tractable mechanism for TMEM175 modulation.American journal of physiology. Cell physiology · 2026Article
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- Distinctive biochemical properties of the μ-opioid receptor-corticotropin- releasing factor CRFPharmacological research · 2025Article
- Molecular mechanism of GIRK2 channel gating modulated by cholesteryl hemisuccinate.Frontiers in physiology · 2024Article
- G protein βγ regulation of KCNQ-encoded voltage-dependent K channels.Frontiers in physiology · 2024Review
- Oxidation Driven Reversal of PIPFunction (Oxford, England) · 2023Article
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- From Crosstalk to Synergism: The Combined Effect of Cholesterol and PI(4,5)PAdvances in experimental medicine and biology · 2023Review
- Use of a Molecular Switch Probe to Activate or Inhibit GIRK1 Heteromers In Silico Reveals a Novel Gating Mechanism.International journal of molecular sciences · 2022Article
- A novel small-molecule selective activator of homomeric GIRK4 channels.The Journal of biological chemistry · 2022Article
- Activity-dependent somatodendritic dopamine release in the substantia nigra autoinhibits the releasing neuron.Cell reports · 2021Article
- Kir Channel Molecular Physiology, Pharmacology, and Therapeutic Implications.Handbook of experimental pharmacology · 2021Review
- Ion Channels of the Islets in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Permeation mechanisms through the selectivity filter and the open helix bundle crossing gate of GIRK2.Computational and structural biotechnology journal · 2020Article
- On the mechanism of GIRK2 channel gating by phosphatidylinositol bisphosphate, sodium, and the Gβγ dimer.The Journal of biological chemistry · 2019Article
- A Comparison of the Ability of LeuMolecular pharmacology · 2019Article
- Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis.The Journal of general physiology · 2018Review
- Dynamic role of the tether helix in PIPThe Journal of general physiology · 2017Article
- The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2.Pflugers Archiv : European journal of physiology · 2016Article
- Article
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Authors and funding
3 authors.
Funding
Abstract
Native and recombinant G protein-gated inwardly rectifying potassium (GIRK) channels are directly activated by the betagamma subunits of GTP-binding (G) proteins. The presence of phosphatidylinositol-bis-phosphate (PIP(2)) is required for G protein activation. Formation (via hydrolysis of ATP) of endogenous PIP(2) or application of exogenous PIP(2) increases the mean open time of GIRK channels and sensitizes them to gating by internal Na(+) ions. In the present study, we show that the activity of ATP- or PIP(2)-modified channels could also be stimulated by intracellular Mg(2+) ions. In addition, Mg(2+) ions reduced the single-channel conductance of GIRK channels, independently of their gating ability. Both Na(+) and Mg(2+) ions exert their gating effects independently of each other or of the activation by the G(betagamma) subunits. At high levels of PIP(2), synergistic interactions among Na(+), Mg(2+), and G(betagamma) subunits resulted in severalfold stimulated levels of channel activity. Changes in ionic concentrations and/or G protein subunits in the local environment of these K(+) channels could provide a rapid amplification mechanism for generation of graded activity, thereby adjusting the level of excitability of the cells.
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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.