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Research Papers
Protein Kinase A Modulates PLC-Dependent Regulation and PIP2-Sensitivity of K+ Channels
Coeli M.B. Lopes, Juan I. Remon, Alessandra Matavel, Jin Liang Sui, Inna Keselman, Emiliano Medei, Yumin Shen, Avia Rosenhouse-Dantsker and Diomedes E. Logothetis
volume 1 | issue 2
March/April 2007Pages: 124 - 134
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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: inwardly-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.
Authors
Coeli M.B. Lopes
Department of Medicine, Cardiovascular Research Institute, University of Rochester, Rochester, NY
Juan I. Remon
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY
Alessandra Matavel
Department of Medicine, Cardiovascular Research Institute, University of Rochester, Rochester, NY
Jin Liang Sui
Mount Sinai School of Medicine, New York, NY
Inna Keselman
Department of Molecular Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY
Emiliano Medei
Department of Medicine, Cardiovascular Research Institute, University of Rochester, Rochester, NY
Yumin Shen
Department of Molecular Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY
Avia Rosenhouse-Dantsker
Mount Sinai School of Medicine, New York, NY
Diomedes E. Logothetis
Mount Sinai School of Medicine, New York, NY
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.