Identification of native rat cerebellar granule cell currents due to background K channel KCNK5 (TASK-2).
The TWIK-related, Acid Sensing K (TASK-2; KCNK5) potassium channel is a member of the tandem pore (2P) family of potassium channels and mediates an alkaline pH-activated, acid pH-inhibited, outward-rectified potassium conductance. In previous work, we demonstrated TASK-2 protein expression in newborn rat cerebellar granule neurons (CGNs). In this study, we demonstrate TASK-2 functional expression in CGNs as a component of the pH-sensitive, volatile anesthetic-potentiated, standing-outward potassium conductance (I(K,SO)). Using excised, inside-out patch-clamp technique, we studied CGNs grown in primary culture. We identified four distinct, noninactivating single channel potassium conductances, Types 1-4. Types 1-3 have previously been attributed to TASK-1 (KCNK3), TASK-3 (KCNK9) and TASK-1/TASK-3 heteromers, and TREK-2 (KCNK10) 2P potassium channel function, respectively; however, the Type 4 conductance is currently unassigned. Previous studies demonstrated that Type 4 single channel activity is potentiated by extracellular, alkaline pH and cytoplasmic arachidonic acid (10-20 microM) and inhibited by cytoplasmic tetraethylammonium (TEA; 1 mM). We determined that heterologously expressed TASK-2 channels have single channel gating, conductance properties and pH sensitivity identical to the Type 4 conductance. Additionally, we found that TASK-2 single channel activity, like the Type 4 conductance is potentiated by cytoplasmic arachidonic acid (20 microM) and inhibited by cytoplasmic TEA (1 mM). We conclude that TASK-2 mediates the Type 4 single channel conductance in CGNs as a component of I(K,SO).
Cotten
Joseph F
JF
Department of Anesthesia and Perioperative Care, University of California, San Francisco, 513 Parnassus Ave., Room S-261, Box 0542, San Francisco, CA 94143, USA.
Zou
Hilary Liao
HL
Liu
Canhui
C
Au
John D
JD
Yost
C Spencer
CS
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000145:classification / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain / Q000302:isolation & purification* / Q000378:metabolism; D051381:Rats; D019789:Tetraethylammonium / Q000494:pharmacology; D014162:Transfection / Q000379:methods
C410295:KCNK5 protein, human; C498740:Kcnk5 protein, rat; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D016718:Arachidonic Acid; D019789:Tetraethylammonium; D011188:Potassium