Inhibition of TASK-1 potassium channel by phospholipase C.
The two-pore-domain K(+) channel, TASK-1, was recently shown to be a target of receptor-mediated regulation in neurons and in adrenal glomerulosa cells. Here, we demonstrate that TASK-1 expressed in Xenopus laevis oocytes is inhibited by different Ca(2+)-mobilizing agonists. Lysophosphatidic acid, via its endogenous receptor, and ANG II and carbachol, via their heterologously expressed ANG II type 1a and M(1) muscarinic receptors, respectively, inhibit TASK-1. This effect can be mimicked by guanosine 5'-O-(3-thiotriphosphate), indicating the involvement of GTP-binding protein(s). The phospholipase C inhibitor U-73122 reduced the receptor-mediated inhibition of TASK-1. Downstream signals of phospholipase C action (inositol 1,4,5-trisphosphate, cytoplasmic Ca(2+) concentration, and diacylglycerol) do not mediate the inhibition. Unlike the G(q)-coupled receptors, stimulation of the G(i)-activating M(2) muscarinic receptor coexpressed with TASK-1 results in an only minimal decrease of the TASK-1 current. However, additional coexpression of phospholipase C-beta(2) (which is responsive also to G(i) beta gamma-subunits) renders M(2) receptor activation effective. This indicates the significance of phospholipase C activity in the receptor-mediated inhibition of TASK-1.
Czirják
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Faculty of Medicine, Laboratory of Cellular and Molecular Physiology, Department of Physiology, Semmelweis University, H-1444 Budapest, Hungary.
Petheo
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GL
Spät
A
A
Enyedi
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D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism / Q000502:physiology*; D000077191:Wortmannin; D014982:Xenopus laevis
D000730:Androstadienes; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011956:Receptors, Cell Surface; C420132:potassium channel subfamily K member 3; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium; D000077191:Wortmannin