TASK-1, a Two-Pore Domain K super(+) Channel, Is Modulated by Multiple Neurotransmitters in Motoneurons

Inhibition of "leak" potassium (K super(+)) channels is a widespread CNS mechanism by which transmitters induce slow excitation. We show that TASK-1, a two pore domain K super(+) channel, provides a prominent leak K super(+) 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 super(+) current with pH- and voltage-dependent properties virtually identical to those of the cloned channel. This pH-sensitive K super(+) 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.