Protein Kinase A Modulates PLC-Dependent Regulation and PIP2-Sensitivity of K+Channels
| Autor: | Emiliano Medei, Diomedes E. Logothetis, Coeli M. Lopes, Juan Remon, Inna Keselman, Jin Liang Sui, Yuming Shen, Alessandra Matavel, Tibor Rohacs, Avia Rosenhouse-Dantsker |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Patch-Clamp Techniques Potassium Channels Xenopus Biophysics Kidney Transfection Biochemistry Cell Line Fluorescence Resonance Energy Transfer Animals Humans Patch clamp Receptor Protein kinase A Microscopy Confocal Dose-Response Relationship Drug Chemistry Inward-rectifier potassium ion channel Hydrolysis Cyclic AMP-Dependent Protein Kinases Acetylcholine Potassium channel Cell biology Electrophysiology Crosstalk (biology) G Protein-Coupled Inwardly-Rectifying Potassium Channels Type C Phospholipases Oocytes Tetradecanoylphorbol Acetate Phosphorylation Female Signal transduction |
| Zdroj: | Channels. 1:124-134 |
| ISSN: | 1933-6969 1933-6950 |
| DOI: | 10.4161/chan.4322 |
| Popis: | Neurotransmitter and hormone regulation of cellular function can result from a concomitant stimulation of different signaling pathways. Signaling cascades are strongly regulated during disease and are often targeted by commonly used drugs. Crosstalk of different signaling pathways can have profound effects on the regulation of cell excitability. Members of all the three main structural families of potassium channels: inward-rectifiers, voltage-gated and 2-P domain, have been shown to be regulated by direct phosphorylation and Gq-coupled receptor activation. Here we test members of each of the three families, Kir3.1/Kir3.4, KCNQ1/KCNE1 and TREK-1 channels, all of which have been shown to be regulated directly by phosphatidylinositol bisphosphate (PIP2). The three channels are inhibited by activation of Gq-coupled receptors and are differentially regulated by protein kinase A (PKA). We show that Gq-coupled receptor regulation can be physiologically modulated directly through specific channel phosphorylation sites. Our results suggest that PKA phosphorylation of these channels affects Gq-coupled receptor inhibition through modulation of the channel sensitivity to PIP2. |
| Databáze: | OpenAIRE |
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