K2P3.1 channels

Channel name K2P3.1
Description Two-pore domain potassium channel subunit; open rectifier
Other names KCNK3, TASK-1, TBAK-1, OAT-1
Molecular information Human: 394aa, NM_002246, chr. 2p24.1-23.3,1 KCNK3,2 GeneID: 3777, PMID: 931200520
Rat: 411aa, NP_203694, kcnk33
Mouse: 409aa, AF065162, chr. 5B,1 kcnk3
Associated subunits 14-3-316,17 and p11 (annexin II subunit),18 see “Comments”
Functional assays Electrophysiological
Current Open rectifier4
Conductance 10pS5
Ion selectivity Rb+ > K+ > Cs+ > NH4+ >> Na+ > Li+
Activation See “Comments”
Inactivation See “Comments”
Activators Volatile anesthetics6,7: halothane (1 mM),5 isofluorane (2 mM)
Gating inhibitors None
Blockers Ba2+ (500 mM), external pH (7.3),8,9,10 arachidonic acid (100 mM) (see “Comments”), and anandamide (3 μM)19
Radioligands None
Channel distribution Brain,11 heart,12 lung, kidney,13 small intestine, colon, pancreas, prostate, uterus, placenta
Physiological functions Not established
Mutations and pathophysiology Not established
Pharmacological significance Not established
Comments Activation and deactivation with voltage steps seems to be instantaneous, but there is also a small, time-dependent change in Po; current is half-blocked at pH 7.3 at physiological external conditions—increasing external potassium decreases proton blockade; pharmacology studies of the rat variant reveal blockade also by zinc, TEA, and quinidine14,15; K2P3-like currents are reported in cerebellar granular neurons and motor-neurons11,15; interaction with 14-3-3 protein is essential for forward trafficking; K2P3 can form heterodimers with K2P9.1 in heterologous expression systems consistent with electrophysiological studies that suggest heterodimerzation; K2P3 is also suggested to be a target for transmitter modulation of neuronal excitability11,15
  • aa, amino acids; chr., chromosome; TEA, tetrylethylammonium.

  • 1. Manjunath NA, Bray-Ward P, Goldstein SAN, and Gallagher PG (1999) Assignment of the 2P domain, acid-sensitive potassium channel gene OAT1 (KCNK3) to human chromosome 2p23.3p24.1 and murine chromosome band 5B by in situ hybridization. Cytogenet Cell Gen 86:242-243

  • 2. Kim D, Fujita A, Horio Y, and Kurachi Y (1998) Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1). Circ Res 82:513-518

  • 3. Leonoudakis D, Gray AT, Winegar BD, Kindler CH, Harada M, Taylor DM, Chavez RA, Forsayeth JR, and Yost CS (1998) An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum. J Neurosci 18:868-877

  • 4. Lopes CMB, Gallagher PG, Wong C, Buck M, and Goldstein SAN (1998) OATs: open, acid-sensitive, two P domain K+ channels from mouse heart. J Biophys 74:A44

  • 5. Washburn CP, Sirois JE, Talley EM, Guyenet PG, and Bayliss DA (2002) Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH- and halothane-sensitive K+ conductance. J Neurosci 22:1256-1265

  • 6. Buckler KJ, Williams BA, and Honoré E (2000) An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemo-receptor cells. J Physiol (Lond) 525:135-142

  • 7. Sirois JE, Lei Q, Talley EM, Lynch C 3rd, and Bayliss DA (2000) The TASK-1 two-pore domain K+ channel is a molecular substrate for neuronal effects of inhalation anesthetics. J Neurosci 20:6347-6354

  • 8. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, and Lazdunski M (1997) TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J 16:5464-5471

  • 9. Lopes CMB, Gallagher PG, Buck ME, Butler MH, and Goldstein SAN (2000) Proton block and voltage-gating are potassium-dependent in the cardiac leak channel kcnk3. J Biol Chem 275:16969-16978

  • 10. Lopes CMB, Zilberberg N, and Goldstein SAN (2001) Block of Kcnk3 by protons: evidence that 2-P-domain potassium channel subunits function as homodimers. J Biol Chem 276:24449-24452

  • 11. Millar JA, Barratt L, Southan AP, Page KM, Fyffe RE, Robertson B, and Mathie A (2000) A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. Proc Natl Acad Sci USA 97:3614-3618

  • 12. Kim Y, Bang H, and Kim D (1999) TBAK-1 and TASK-1, two-pore K(+) channel subunits: kinetic properties and expression in rat heart. Am J Physiol 277:H1669-H1678

  • 13. Czirjak G, Fischer T, Spat A, Lesage F, and Enyedi P (2000) TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II. Mol Endocrinol 14:863-874

  • 14. Kindler CH, Yost CS, and Gray AT (1999) Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem. Anesthesiology 90:1092-1102

  • 15. Talley EM, Lei QB, Sirois JE, and Bayliss DA (2000) TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. Neuron 25:399-410

  • 16. Rajan S, Preisig-Muller R, Wischmeyer E, Nehring R, Hanley PJ, Renigunta V, Musset B, Schlichthorl G, Derst C, Karschin A, et al. (2002) Interaction with 14-3-3proteins promotes functional expression of the potassium channels TASK-1 and TASK-3. J Physiol 545:13-26

  • 17. O'Kelly I, Butler MH, Zilberberg N, and Goldstein SA (2002) Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals. Cell 111:577-588

  • 18. Girard C, Tinel N, Terrenoire C, Romey G, Lazdunski M, and Borsotto M (2002) p11, an annexin II subunit, an auxiliary protein associated with the background K+ channel, TASK-1. EMBO J 21:4439-4448

  • 19. Maingret F, Patel AJ, Lazdunski M, and Honoré E (2001) The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1. EMBO J 15:47-54

  • 20. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, and Lazdunski M (1997) TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J 16:5464-5471