TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons

Neuron. 2000 Feb;25(2):399-410. doi: 10.1016/s0896-6273(00)80903-4.

Abstract

Inhibition of "leak" potassium (K+) channels is a widespread CNS mechanism by which transmitters induce slow excitation. We show that TASK-1, a two pore domain K+ channel, provides a prominent leak K+ current and target for neurotransmitter modulation in hypoglossal motoneurons (HMs). TASK-1 mRNA is present at high levels in motoneurons, including HMs, which express a K+ current with pH- and voltage-dependent properties virtually identical to those of the cloned channel. This pH-sensitive K+ channel was fully inhibited by serotonin, norepinephrine, substance P, thyrotropin-releasing hormone, and 3,5-dihydroxyphenylglycine, a group I metabotropic glutamate receptor agonist. The neurotransmitter effect was entirely reconstituted in HEK 293 cells coexpressing TASK-1 and the TRH-R1 receptor. Given its expression patterns and the widespread prevalence of this neuromodulatory mechanism, TASK-1 also likely supports this action in other CNS neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acids / pharmacology
  • Animals
  • Animals, Newborn
  • Cell Line
  • Electric Conductivity
  • Gene Expression / physiology
  • Glutamic Acid / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Hypoglossal Nerve / cytology
  • Kidney / cytology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Motor Neurons / chemistry
  • Motor Neurons / metabolism*
  • Nerve Tissue Proteins
  • Neurotransmitter Agents / metabolism*
  • Norepinephrine / metabolism
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Tandem Pore Domain*
  • Protein Structure, Tertiary
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Substance P / metabolism
  • Thyrotropin-Releasing Hormone / metabolism
  • Transfection

Substances

  • Acids
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • RNA, Messenger
  • potassium channel subfamily K member 3
  • Serotonin
  • Substance P
  • Glutamic Acid
  • Thyrotropin-Releasing Hormone
  • Potassium
  • Norepinephrine