ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Probing the regulation of M (Kv7) potassium channels in intact neurons with membrane-targeted peptides.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 54 citations in OpenAlex.
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- Involvement of CaCellular and molecular neurobiology · 2023Article
- A network of phosphatidylinositol (4,5)-bisphosphate (PIPMolecular psychiatry · 2021Article
- Identification of N-arachidonoyl dopamine as a highly biased ligand at cannabinoid CB1 receptors.British journal of pharmacology · 2016Article
- Phosphoinositide Modulation of Heteromeric Kv1 Channels Adjusts Output of Spiral Ganglion Neurons from Hearing Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Phosphoinositide control of membrane protein function: a frontier led by studies on ion channels.Annual review of physiology · 2015Review
- Pepducins and Other Lipidated Peptides as Mechanistic Probes and Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2015Article
- PIP2 regulates psychostimulant behaviors through its interaction with a membrane protein.Nature chemical biology · 2014Article
- The actions of Pasteurella multocida toxin on neuronal cells.Neuropharmacology · 2014Article
- Amphetamine actions at the serotonin transporter rely on the availability of phosphatidylinositol-4,5-bisphosphate.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Tamoxifen inhibition of kv7.2/kv7.3 channels.PloS one · 2013Article
- Voltage-dependent open-channel block of G protein-gated inward-rectifying K(+) (GIRK) current in rat atrial myocytes by tamoxifen.Naunyn-Schmiedeberg's archives of pharmacology · 2012Article
- Turning receptors on and off with intracellular pepducins: new insights into G-protein-coupled receptor drug development.The Journal of biological chemistry · 2012Review
- Channelopathies linked to plasma membrane phosphoinositides.Pflugers Archiv : European journal of physiology · 2010Review
- Cholesterol inhibits M-type K+ channels via protein kinase C-dependent phosphorylation in sympathetic neurons.The Journal of biological chemistry · 2010Article
- Ca2+/calmodulin disrupts AKAP79/150 interactions with KCNQ (M-Type) K+ channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Affinity for phosphatidylinositol 4,5-bisphosphate determines muscarinic agonist sensitivity of Kv7 K+ channels.The Journal of general physiology · 2009Article
- Regulation of wild-type and mutant KCNQ1/KCNE1 channels by tyrosine kinase.Pflugers Archiv : European journal of physiology · 2009Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
M-type (Kv7) potassium channels are closed by Gq/11 G-protein-coupled receptors. Several membrane- or channel-associated molecules have been suggested to contribute to this effect, including depletion of phosphatidylinositol-4,5-bisphosphate (PIP2) and activation of Ca2+/calmodulin and protein kinase C. To facilitate further study of these pathways in intact neurons, we have devised novel membrane-targeted probes that can be applied from the outside of the neuron, by attaching a palmitoyl group to site-directed peptides ("palpeptides") (cf. Covic et al., 2002a,b). A palpeptide incorporating the 10-residue C terminus of Galphaq/11 reduced Gq/11-mediated M-current inhibition in sympathetic neurons by the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine-M but not Go-mediated inhibition of the N-type Ca2+ current by norepinephrine. Instead, the latter was inhibited by the corresponding Go palpeptide. A PIP2 palpeptide, based on the putative PIP2 binding domain of the Kv7.2 channel, inhibited M current (IC50 = approximately 1.5 microm) and enhanced inhibition by oxotremorine-M. Inhibition could not be attributed to activation of mAChRs, calcium influx, or block of M channels but was antagonized by intracellular diC8-PIP2 (dioctanoyl-phosphatidylinositol-4,5-bisphosphate), suggesting that it disrupted PIP2-M channel gating. A fluorescently tagged PIP2 palpeptide was highly targeted to the plasma membrane but did not accumulate in the cytoplasm. We suggest that these palpeptides are anchored in the plasma membrane via the palmitoyl group, such that the peptide moiety can interact with target molecules on the inner face of the membrane. The G-protein-replicating palpeptides were sequence specific and probably compete with the receptor for the cognate G-protein. The PIP2 palpeptide was not sequence specific so probably interacts electrostatically with anionic PIP2 head groups.
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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.