1. Diacylglycerol mediates regulation of TASK potassium channels by Gq-coupled receptors
- Author
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Moritz Lindner, Alexandra Albus, Lea Greifenberg, Yannick Kronimus, Dominik Oliver, Moritz Bünemann, Michael G. Leitner, and Bettina U. Wilke
- Subjects
Phosphatidylinositol 4,5-Diphosphate ,Amino Acid Motifs ,General Physics and Astronomy ,Nerve Tissue Proteins ,Inositol 1,4,5-Trisphosphate ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Diglycerides ,Mice ,Potassium Channels, Tandem Pore Domain ,Animals ,Humans ,Receptor ,Protein Kinase C ,Diacylglycerol kinase ,Multidisciplinary ,urogenital system ,General Chemistry ,GTP-Binding Protein alpha Subunits ,Potassium channel ,Cell biology ,Biochemistry ,Type C Phospholipases ,Second messenger system ,Cellular excitability ,GTP-Binding Protein alpha Subunits, Gq-G11 ,Calcium ,lipids (amino acids, peptides, and proteins) ,Signal Transduction - Abstract
The two-pore domain potassium (K2P) channels TASK-1 (KCNK3) and TASK-3 (KCNK9) are important determinants of background K(+) conductance and membrane potential. TASK-1/3 activity is regulated by hormones and transmitters that act through G protein-coupled receptors (GPCR) signalling via G proteins of the Gαq/11 subclass. How the receptors inhibit channel activity has remained unclear. Here, we show that TASK-1 and -3 channels are gated by diacylglycerol (DAG). Receptor-initiated inhibition of TASK required the activity of phospholipase C, but neither depletion of the PLC substrate PI(4,5)P2 nor release of the downstream messengers IP3 and Ca(2+). Attenuation of cellular DAG transients by DAG kinase or lipase suppressed receptor-dependent inhibition, showing that the increase in cellular DAG-but not in downstream lipid metabolites-mediates channel inhibition. The findings identify DAG as the signal regulating TASK channels downstream of GPCRs and define a novel role for DAG that directly links cellular DAG dynamics to excitability.
- Published
- 2014