TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons.
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.
Talley
E M
EM
Department of Pharmacology, University of Virginia, Charlottesville 22908, USA. emt3m@virginia.edu
Lei
Q
Q
Sirois
J E
JE
Bayliss
D A
DA
D000143:Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D004553:Electric Conductivity; D015870:Gene Expression / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007002:Hypoglossal Nerve / Q000166:cytology; D007668:Kidney / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism; D014162:Transfection
D000143:Acids; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C420132:potassium channel subfamily K member 3; D012701:Serotonin; D013373:Substance P; D018698:Glutamic Acid; D013973:Thyrotropin-Releasing Hormone; D011188:Potassium; D009638:Norepinephrine