An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum.
Tandem pore domain K+ channels represent a new family of ion channels involved in the control of background membrane conductances. We report the structural and functional properties of a TWIK-related acid-sensitive K+ channel (rTASK), a new member of this family cloned from rat cerebellum. The salient features of the primary amino acid sequence include four putative transmembrane domains and, unlike other cloned tandem pore domain channels, a PDZ (postsynaptic density protein, disk-large, zo-1) binding sequence at the C terminal. rTASK has distant overall homology to a putative Caenorhabditis elegans K+ channel and to the mammalian clones TREK-1 and TWIK-1. rTASK expression is most abundant in rat heart, lung, and brain. When exogenously expressed in Xenopus oocytes, rTASK currents activate instantaneously, are noninactivating, and are not gated by voltage. Because rTASK currents satisfy the Goldman-Hodgkin-Katz current equation for an open channel, rTASK can be classified an open rectifier. Activation of protein kinase A produces inhibition of rTASK, whereas activation of protein kinase C has no effect. rTASK currents were inhibited by extracellular acidity. rTASK currents also were inhibited by Zn2+ (IC50 = 175 microM), the local anesthetic bupivacaine (IC50 = 68 microM), and the anti-convulsant phenytoin ( approximately 50% inhibition at 200 microM). By demonstrating open rectification and open probability independent of voltage, we have established that rTASK is a baseline potassium channel.
Leonoudakis
D
D
Department of Anesthesia, University of California San Francisco, San Francisco, California 94143-0542, USA.
Gray
A T
AT
Winegar
B D
BD
Kindler
C H
CH
Harada
M
M
Taylor
D M
DM
Chavez
R A
RA
Forsayeth
J R
JR
Yost
C S
CS
D000143:Acids; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D015152:Blotting, Northern; D002045:Bupivacaine / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002531:Cerebellum / Q000737:chemistry*; D003001:Cloning, Molecular; D000431:Ethanol / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008012:Lidocaine / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010766:Phosphorylation; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019789:Tetraethylammonium / Q000494:pharmacology; D014981:Xenopus; D015032:Zinc / Q000494:pharmacology
D000143:Acids; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D002492:Central Nervous System Depressants; D010455:Peptides; D015221:Potassium Channels; D012333:RNA, Messenger; D001464:Barium; C008331:mast cell degranulating peptide; D000431:Ethanol; D010672:Phenytoin; D019789:Tetraethylammonium; D008012:Lidocaine; D008274:Magnesium; D011802:Quinidine; D015032:Zinc; D002045:Bupivacaine