Inhibition of TASK-1 potassium channel by phospholipase C

Am J Physiol Cell Physiol. 2001 Aug;281(2):C700-8. doi: 10.1152/ajpcell.2001.281.2.C700.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Calcium / physiology
  • Electric Conductivity
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • Female
  • GTP-Binding Proteins / metabolism
  • GTP-Binding Proteins / physiology
  • Inositol 1,4,5-Trisphosphate / physiology
  • Nerve Tissue Proteins*
  • Oocytes / metabolism
  • Potassium Channel Blockers*
  • Potassium Channels / physiology
  • Potassium Channels, Tandem Pore Domain*
  • Protein Kinase C / physiology
  • Protein-Tyrosine Kinases / physiology
  • Receptors, Cell Surface / physiology
  • Type C Phospholipases / metabolism
  • Type C Phospholipases / physiology*
  • Wortmannin
  • Xenopus laevis


  • Androstadienes
  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • Receptors, Cell Surface
  • potassium channel subfamily K member 3
  • Inositol 1,4,5-Trisphosphate
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Type C Phospholipases
  • GTP-Binding Proteins
  • Calcium
  • Wortmannin