Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH- and halothane-sensitive K+ conductance.
The recently described two-pore-domain K+ channels, TASK-1 and TASK-3, generate currents with a unique set of properties; specifically, the channels produce instantaneous open-rectifier (i.e., "leak") K+ currents that are modulated by extracellular pH and by clinically useful anesthetics. In this study, we used histochemical and in vitro electrophysiological approaches to determine that TASK channels are expressed in serotonergic raphe neurons and to show that they confer a pH and anesthetic sensitivity to these neurons. By combining in situ hybridization for TASK-1 or TASK-3 with immunohistochemical localization of tryptophan hydroxylase, we found that a majority of serotonergic neurons in both dorsal and caudal raphe cell groups contain TASK channel transcripts (approximately 70-90%). Whole-cell voltage-clamp recordings were obtained from raphe cells that responded to 5-HT in a manner characteristic of serotonergic neurons (i.e., with activation of an inwardly rectifying K+ current). In those cells, we isolated an endogenous K+ conductance that had properties expected of TASK channel currents; raphe neurons expressed a joint pH- and halothane-sensitive open-rectifier K+ current. The pH sensitivity of this current (pK approximately 7.0) was intermediate between that of TASK-1 and TASK-3, consistent with functional expression of both channel types. Together, these data indicate that TASK-1 and TASK-3 are expressed and functional in serotonergic raphe neurons. The pH-dependent inhibition of TASK channels in raphe neurons may contribute to ventilatory and arousal reflexes associated with extracellular acidosis; on the other hand, activation of raphe neuronal TASK channels by volatile anesthetics could play a role in their immobilizing and sedative-hypnotic effects.
Washburn
Christopher P
CP
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908-0735, USA.
Sirois
Jay E
JE
Talley
Edmund M
EM
Guyenet
Patrice G
PG
Bayliss
Douglas A
DA
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger / Q000096:biosynthesis; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*
C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C420132:potassium channel subfamily K member 3; D012701:Serotonin; D011188:Potassium; D006221:Halothane