Abstract
A number of tandem P-domain K+- channels (K2P) generate background K+-currents similar to those found in enteroreceptors that sense a diverse range of physiological stimuli including blood pH, carbon dioxide, oxygen, potassium and glucose. This review presents an overview of the properties of both cloned K2P tandem-P-domain K-channels and the endogenous chemosensitive background K-currents found in central chemoreceptors, peripheral chemoreceptors, the adrenal gland and the hypothalamus. Although the identity of many of these endogenous channels has yet to be confirmed they show striking similarities to a number of K2P channels especially those of the TASK subgroup. Moreover these channels seem often (albeit not exclusively) to be involved in pH and nutrient/metabolic sensing.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hodgkin AL, Huxley AF (1952) The components of membrane conductance in the giant axon of Loligo. J Physiol 116:473-496
Ketchum KA, Joiner WJ, Sellers AJ, Kaczmarek LK, Goldstein SA (1995) A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature 376:690-695
Wei A, Jegla T, Salkoff L (1996) Eight potassium channel families revealed by the C. elegans genome project. Neuropharmacology 35:805-829
Lesage F, Guillemare E, Fink M et al (1996) TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J 15:1004-1011
Lesage F, Reyes R, Fink M, Duprat F, Guillemare E, Lazdunski M (1996) Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge. EMBO J 15:6400-6407
Berg AP, Talley EM, Manger JP, Bayliss DA (2004) Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. J Neurosci 24:6693-6702
Czirjak G, Enyedi P (2002) Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits. J Biol Chem 277:5426-5432
Kang D, Han J, Talley EM, Bayliss DA, Kim D (2004) Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. J Physiol 554:64-77
Clarke CE, Veale EL, Wyse K, Vandenberg JI, Mathie A (2008) The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function. J Biol Chem 283:16985-16992
Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (2005) International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels. Pharmacol Rev 57:527-540
Lesage F (2003) Pharmacology of neuronal background potassium channels. Neuropharmacology 44:1-7
Bayliss DA, Barrett PQ (2008) Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact. Trends Pharmacol Sci 29:566-575
Talley EM, Sirois JE, Lei Q, Bayliss DA (2003) Two-pore-Domain (KCNK) potassium channels: dynamic roles in neuronal function. Neuroscientist 9:46-56
Maingret F, Honore E, Lazdunski M, Patel AJ (2002) Molecular basis of the voltage-dependent gating of TREK-1, a mechano-sensitive K+ channel. Biochem Biophys Res Commun 292:339-346
Bockenhauer D, Zilberberg N, Goldstein SA (2001) KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nat Neurosci 4:486-491
Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M (1997) TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J 16:5464-5471
Lopes CM, Gallagher PG, Buck ME, Butler MH, Goldstein SA (2000) Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. J Biol Chem 275:16969-16978
Kim Y, Bang H, 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
Rajan S, Wischmeyer E, Xin Liu G et al (2000) TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor. J Biol Chem 275:16650-16657
Kim Y, Bang H, Kim D (2000) TASK-3, a new member of the tandem pore K+ channel family. J Biol Chem 275:9340-9347
Chapman CG, Meadows HJ, Godden RJ et al (2000) Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel. Brain Res Mol Brain Res 82:74-83
Meadows HJ, Randall AD (2001) Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel. Neuropharmacology 40:551-559
Han J, Kang D, Kim D (2003) Functional properties of four splice variants of a human pancreatic tandem-pore K+ channel, TALK-1. Am J Physiol Cell Physiol 285:C529-C538
Reyes R, Duprat F, Lesage F et al (1998) Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J Biol Chem 273:30863-30869
Decher N, Maier M, Dittrich W et al (2001) Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family. FEBS Lett 492:84-89
Girard C, Duprat F, Terrenoire C et al (2001) Genomic and functional characteristics of novel human pancreatic 2P domain K+ channels. Biochem Biophys Res Commun 282:249-256
Rajan S, Plant LD, Rabin ML, Butler MH, Goldstein SA (2005) Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell 121:37-47
Sano Y, Inamura K, Miyake A et al (2003) A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord. J Biol Chem 278:27406-27412
Patel AJ, Maingret F, Magnone V, Fosset M, Lazdunski M, Honore E (2000) TWIK-2, an inactivating 2P domain K+ channel. J Biol Chem 275:28722-28730
Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (1999) Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 274:26691-26696
Honore E, Maingret F, Lazdunski M, Patel AJ (2002) An intracellular proton sensor commands lipid- and mechano-gating of the K+ channel TREK-1. EMBO J 21:2968-2976
Chavez RA, Gray AT, Zhao BB et al (1999) TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium channel family. J Biol Chem 274:7887-7892
Maingret F, Lauritzen I, Patel AJ et al (2000) TREK-1 is a heat-activated background K+ channel. EMBO J 19:2483-2491
Kang D, Choe C, Kim D (2005) Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. J Physiol 564:103-116
Patel AJ, Honore E, Maingret F et al (1998) A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J 17:4283-4290
Bang H, Kim Y, Kim D (2000) TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. J Biol Chem 275:17412-17419
Fink M, Lesage F, Duprat F et al (1998) A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J 17:3297-3308
Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (2000) Lysophospholipids open the two-pore domain mechano-gated K+ channels TREK-1 and TRAAK. J Biol Chem 275:10128-10133
Patel AJ, Lazdunski M, Honore E (2001) Lipid and mechano-gated 2P domain K+ channels. Curr Opin Cell Biol 13:422-428
Rajan S, Wischmeyer E, Karschin C et al (2001) THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels. J Biol Chem 276:7302-7311
Patel AJ, Honore E (2001) Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci 24:339-346
Maingret F, Fosset M, Lesage F, Lazdunski M, Honore E (1999) TRAAK is a mammalian neuronal mechano-gated K+ channel. J Biol Chem 274:1381-1387
Lesage F, Terrenoire C, Romey G, Lazdunski M (2000) Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. J Biol Chem 275:28398-28405
Lesage F, Maingret F, Lazdunski M (2000) Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K+ channel. FEBS Lett 471:137-140
Patel AJ, Honore E, Lesage F, Fink M, Romey G, Lazdunski M (1999) Inhalational anesthetics activate two-pore-domain background K+ channels. Nat Neurosci 2:422-426
Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP (2004) Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol 65:443-452
Patel AJ, Honore E (2001) Anesthetic-sensitive 2P domain K+ channels. Anesthesiology 95:1013-1021
Franks NP, Honore E (2004) The TREK K2P channels and their role in general anaesthesia and neuroprotection. Trends Pharmacol Sci 25:601-608
Heurteaux C, Guy N, Laigle C et al (2004) TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J 23:2684-2695
Andres-Enguix I, Caley A, Yustos R et al (2007) Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive potassium channels: molecular cloning of an anesthetic-activated potassium channel from Lymnaea stagnalis. J Biol Chem 282:20977-20990
Putzke C, Hanley PJ, Schlichthorl G et al (2007) Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1. Am J Physiol Cell Physiol 293:C1319-C1326
Liu C, Au JD, Zou HL, Cotten JF, Yost CS (2004) Potent activation of the human tandem pore domain K channel TRESK with clinical concentrations of volatile anesthetics. Anesth Analg 99:1715-1722
Maingret F, Patel AJ, Lazdunski M, Honore E (2001) The endocannabinoid anandamide is a direct and selective blocker of the background K+ channel TASK-1. EMBO J 20:47-54
Czirjak G, Enyedi P (2003) Ruthenium red inhibits TASK-3 potassium channel by interconnecting glutamate 70 of the two subunits. Mol Pharmacol 63:646-652
Clarke CE, Veale EL, Green PJ, Meadows HJ, Mathie A (2004) Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc. J Physiol 560:51-62
Bautista DM, Sigal YM, Milstein AD et al (2008) Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels. Nat Neurosci 11:772-779
Czirjak G, Enyedi P (2006) Zinc and mercuric ions distinguish TRESK from the other two-pore-domain K+ channels. Mol Pharmacol 69:1024-1032
Nattie E (2006) Why do we have both peripheral and central chemoreceptors? J Appl Physiol 100:9-10
Smith CA, Rodman JR, Chenuel BJ, Henderson KS, Dempsey JA (2006) Response time and sensitivity of the ventilatory response to CO2 in unanesthetized intact dogs: central vs. peripheral chemoreceptors. J Appl Physiol 100:13-19
Nattie E, Li A (2006) Central chemoreception 2005: a brief review. Auton Neurosci 126-127:332-338
Guyenet PG, Bayliss DA, Mulkey DK, Stornetta RL, Moreira TS, Takakura AT (2008) The retrotrapezoid nucleus and central chemoreception. Adv Exp Med Biol 605:327-332
Wellner-Kienitz MC, Shams H (1998) Hyperpolarization-activated inward currents contribute to spontaneous electrical activity and CO2/H+ sensitivity of cultivated neurons of fetal rat medulla. Neuroscience 87:109-121
Sirois JE, Lei Q, Talley EM, Lynch C 3rd, 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
Oyamada Y, Ballantyne D, Muckenhoff K, Scheid P (1998) Respiration-modulated membrane potential and chemosensitivity of locus coeruleus neurones in the in vitro brainstem-spinal cord of the neonatal rat. J Physiol 513:381-398
Bayliss DA, Talley EM, Sirois JE, Lei Q (2001) TASK-1 is a highly modulated pH-sensitive ‘leak’ K+ channel expressed in brainstem respiratory neurons. Respir Physiol 129:159-174
Wang W, Tiwari JK, Bradley SR, Zaykin RV, Richerson GB (2001) Acidosis-stimulated neurons of the medullary raphe are serotonergic. J Neurophysiol 85:2224-2235
Washburn CP, Sirois JE, Talley EM, Guyenet PG, 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
Mulkey DK, Talley EM, Stornetta RL et al (2007) TASK channels determine pH sensitivity in select respiratory neurons but do not contribute to central respiratory chemosensitivity. J Neurosci 27:14049-14058
Mulkey DK, Stornetta RL, Weston MC et al (2004) Respiratory control by ventral surface chemoreceptor neurons in rats. Nat Neurosci 7:1360-1369
Buckler KJ, Vaughan Jones RD (1994) Effects of hypoxia on membrane potential and intracellular calcium in rat neonatal carotid body type I cells. J Physiol 476:423-428
Buckler KJ, Vaughan Jones RD (1994) Effects of hypercapnia on membrane potential and intracellular calcium in rat carotid body type I cells. J Physiol 478:157-171
Rocher A, Geijo Barrientos E, Caceres AI, Rigual R, Gonzalez C, Almaraz L (2005) Role of voltage-dependent calcium channels in stimulus-secretion coupling in rabbit carotid body chemoreceptor cells. J Physiol 562:407-420
Weir EK, Lopez-Barneo J, Buckler KJ, Archer SL (2005) Acute oxygen-sensing mechanisms. N Engl J Med 353:2042-2055
Gonzalez C, Almaraz L, Obeso A, Rigual R (1992) Oxygen and acid chemoreception in the carotid body chemoreceptors. Trends Neurosci 15:146-153
Montoro RJ, Urena J, Fernandez Chacon R, Alvarez de Toledo G, Lopez Barneo J (1996) Oxygen sensing by ion channels and chemotransduction in single glomus cells. J Gen Physiol 107:133-143
Buckler KJ (1997) A novel oxygen-sensitive potassium current in rat carotid body type I cells. J Physiol 498:649-662
Buckler KJ, Williams BA, Honore E (2000) An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells. J Physiol 525:135-142
Ponte J, Sadler CL (1989) Effect of halothane, enflurane and isoflurane on carotid body chemoreceptor activity in the rabbit and the cat. Br J Anaesth 62:33-40
Davies RO, Edwards MW Jr, Lahiri S (1982) Halothane depresses the response of carotid body chemoreceptors to hypoxia and hypercapnia in the cat. Anesthesiology 57:153-159
Knill RL, Gelb AW (1978) Ventilatory responses to hypoxia and hypercapnia during halothane sedation and anesthesia in man. Anesthesiology 49:244-251
Pandit JJ (2002) The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans: a quantitative review. Anaesthesia 57:632-643
Williams BA, Buckler KJ (2004) Biophysical properties and metabolic regulation of a TASK-like potassium channel in rat carotid body type 1 cells. Am J Physiol Lung Cell Mol Physiol 286:L221-L230
Yamamoto K, Kummer W, Atoji Y, Suzuki Y (2002) TASK-1, TASK-2, TASK-3 and TRAAK immunoreactivities in the rat carotid body. Brain Res 950:304-307
Kim I, Kim JH, Carroll JL (2006) Postnatal changes in gene expression of subfamilies of TASK K+ channels in rat carotid body. Adv Exp Med Biol 580:43-47
Yamamoto Y, Taniguchi K (2006) Immunolocalization of tandem pore domain K+ channels in the rat carotid body. Adv Exp Med Biol 580:9-14
Wilson DF, Mokashi A, Chugh D, Vinogradov S, Osanai S, Lahiri S (1994) The primary oxygen sensor of the cat carotid body is cytochrome a3 of the mitochondrial respiratory chain. FEBS Lett 351:370-374
Anichkov S, Belen’kii M (1963) Pharmacology of the carotid body chemoreceptors. Pergamon, Oxford, UK
Mulligan E, Lahiri S, Storey BT (1981) Carotid body O2 chemoreception and mitochondrial oxidative phosphorylation. J Appl Physiol 51:438-446
Shen TCR, Hauss WH (1939) Influence of dinitrophenol, dinitroortocresol and paranitrophenol upon the carotid sinus chemoreceptors of the dog. Arch. Int Pharmacodyn Ther 63:251-258
Biscoe TJ, Duchen MR (1990) Responses of type I cells dissociated from the rabbit carotid body to hypoxia. J Physiol 428:39-59
Mosqueria M, Iturriaga R (2002) Carotid body chemosensory excitation induced by nitric oxide: involvement of oxidative metabolism. Respir Physiol Neurobiol 131:175-187
Mulligan E, Lahiri S (1981) Dependence of carotid chemoreceptor stimulation by metabolic agents on PaO2 and PaCO2. J Appl Physiol 50:884-891
Obeso A, Almaraz L, Gonzalez C (1989) Effects of cyanide and uncouplers on chemoreceptor activity and ATP content of the cat carotid body. Brain Res 481:250-257
Ortega-Sáenz P, Pardal R, Garcáa Fernández M, López Barneo J (2003) Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells. J Physiol 548:789-800
Buckler KJ, Vaughan Jones RD (1998) Effects of mitochondrial uncouplers on intracellular calcium, pH and membrane potential in rat carotid body type I cells. J Physiol 513:819-833
Wyatt CN, Buckler KJ (2004) The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J Physiol 556:175-191
Varas R, Wyatt CN, Buckler KJ (2007) Modulation of TASK-like background potassium channels in rat arterial chemoreceptor cells by intracellular ATP and other nucleotides. J Physiol 583:521-536
Wyatt CN, Kumar P, Aley P, Peers C, Hardie DG, Evans AM (2006) Does AMP-activated protein kinase couple hypoxic inhibition of oxidative phosphorylation to carotid body excitation? Adv Exp Med Biol 580:191-196
Prabhakar NR (2006) O2 sensing at the mammalian carotid body: why multiple O2 sensors and multiple transmitters? Exp Physiol 91:17-23
Lotshaw DP (2001) Role of membrane depolarization and T-type Ca2+ channels in angiotensin II and K+ stimulated aldosterone secretion. Mol Cell Endocrinol 175:157-171
Balla T, Varnai P, Hollo Z, Spat A (1990) Effects of high potassium concentration and dihydropyridine Ca2+-channel agonists on cytoplasmic Ca2+ and aldosterone production in rat adrenal glomerulosa cells. Endocrinology 127:815-822
Lotshaw DP (1997) Characterization of angiotensin II-regulated K+ conductance in rat adrenal glomerulosa cells. J Membr Biol 156:261-277
Spat A (2004) Glomerulosa cell — a unique sensor of extracellular K+ concentration. Mol Cell Endocrinol 217:23-26
Lotshaw DP (2006) Biophysical and pharmacological characteristics of native two-pore domain TASK channels in rat adrenal glomerulosa cells. J Membr Biol 210:51-70
Czirjak G, Fischer T, Spat A, Lesage F, 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
Czirjak G, Enyedi P (2002) TASK-3 dominates the background potassium conductance in rat adrenal glomerulosa cells. Mol Endocrinol 16:621-629
Heitzmann D, Derand R, Jungbauer S et al (2008) Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and mineralocorticoid homeostasis. EMBO J 27:179-187
Davies LA, Hu C, Guagliardo NA et al (2008) TASK channel deletion in mice causes primary hyperaldosteronism. Proc Natl Acad Sci U S A 105:2203-2208
Enyeart JJ, Xu L, Danthi S, Enyeart JA (2002) An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1. J Biol Chem 277:49186-49199
Enyeart JA, Danthi SJ, Enyeart JJ (2004) TREK-1 K+ channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells. Am J Physiol Endocrinol Metab 287:E1154-E1165
Danthi S, Enyeart JA, Enyeart JJ (2003) Modulation of native TREK-1 and Kv1.4 K+ channels by polyunsaturated fatty acids and lysophospholipids. J Membr Biol 195:147-164
Burdakov D, Jensen LT, Alexopoulos H et al (2006) Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose. Neuron 50:711-722
Gonzalez JA, Jensen LT, Fugger L, Burdakov D (2008) Metabolism-independent sugar sensing in central orexin neurons. Diabetes 57:2569-2576
Williams RH, Jensen LT, Verkhratsky A, Fugger L, Burdakov D (2007) Control of hypothalamic orexin neurons by acid and CO2. Proc Natl Acad Sci U S A 104:10685-10690
Kuwaki T (2008) Orexinergic modulation of breathing across vigilance states. Respir Physiol Neurobiol 164:204-212
Olschewski A, Li Y, Tang B et al (2006) Impact of TASK-1 in human pulmonary artery smooth muscle cells. Circ Res 98:1072-1080
Warth R, Barriere H, Meneton P et al (2004) Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport. Proc Natl Acad Sci U S A 101:8215-8220
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Humana Press, a part of Springer Science+Business Media, LLC
About this paper
Cite this paper
Buckler, K.J. (2010). Two-Pore Domain K+ Channels and Their Role in Chemoreception. In: Yuan, JJ., Ward, J. (eds) Membrane Receptors, Channels and Transporters in Pulmonary Circulation. Advances in Experimental Medicine and Biology, vol 661. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-500-2_2
Download citation
DOI: https://doi.org/10.1007/978-1-60761-500-2_2
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-499-9
Online ISBN: 978-1-60761-500-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)