Striatal cholinergic interneurons express a receptor-insensitive homomeric TASK-3-like background K+ current.
Large aspiny cholinergic interneurons provide the sole source of striatal acetylcholine, a neurotransmitter essential for normal basal ganglia function. Cholinergic interneurons engage in multiple firing patterns that depend on interactions among various voltage-dependent ion channels active at different membrane potentials. Leak conductances, particularly leak K(+) channels, are of primary importance in establishing the prevailing membrane potential. We have combined molecular neuroanatomy with whole cell electrophysiology to demonstrate that TASK-3 (K(2P)9.1, Kcnk9) subunits contribute to leak K(+) currents in striatal cholinergic interneurons. Immunostaining for choline acetyltransferase was combined with TASK-3 labeling, using nonradioactive cRNA probes or antisera selective for TASK-3, to demonstrate that striatal cholinergic neurons universally express TASK-3. Consistent with this, we isolated a pH-, anesthetic-, and Zn(2+)-sensitive current with properties expected of TASK-3 homodimeric channels. Surprisingly, activation of Galphaq-linked receptors (metabotropic glutamate mGluR1/5 or histamine H1) did not appear to modulate native interneuron TASK-3-like currents. Together, our data indicate that homomeric TASK-3-like background K(+) currents contribute to establishing membrane potential in striatal cholinergic interneurons and they suggest that receptor modulation of TASK channels is dependent on cell context.
Berg
Allison P
AP
Department of Pharmacology, 5015 Jordan Hall, University of Virginia, Charlottesville, VA 22908, USA. apb6w@virginia.edu
Bayliss
Douglas A
DA
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000494:pharmacology
C407082:Kcnk9 protein, rat; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D002795:Choline O-Acetyltransferase; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D015032:Zinc