Skip to main content

Advertisement

SpringerLink
Log in

Two-Pore Domain Potassium Channel in Neurological Disorders

  • Topical Review
  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

A Correction to this article was published on 22 March 2022

This article has been updated

Abstract

K2P channel is the leaky potassium channel that is critical to keep up the negative resting membrane potential for legitimate electrical conductivity of the excitable tissues. Recently, many substances and medication elements are discovered that could either straightforwardly or in a roundabout way influence the 15 distinctive K+ ion channels including TWIK, TREK, TASK, TALK, THIK, and TRESK. Opening and shutting of these channels or any adjustment in their conduct is thought to alter the pathophysiological condition of CNS. There is no document available till now to explain in detail about the molecular mechanism of agents acting on K2P channel. Accordingly, in this review we cover the current research and mechanism of action of these channels, we have also tried to mention the detailed effect of drugs and how the channel behavior changes by focusing on recent advances regarding activation and modulation of ion channels.

Graphic Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Change history

References

  • Abraham DM, Lee TE, Watson LJ, Mao L, Chandok G, Wang HG, Frangakis S, Pitt GS, Shah SH, Wolf MJ, Rockman HA (2018) The two-pore domain potassium channel TREK-1 mediates cardiac fibrosis and diastolic dysfunction. J Clin Invest 128:4843–4855

    Article  PubMed  PubMed Central  Google Scholar 

  • Acosta C, Djouhri L, Watkins R, Berry C, Bromage K, Lawson SN (2014) TREK2 expressed selectively in IB4-binding C-fiber nociceptors hyperpolarizes their membrane potentials and limits spontaneous pain. J Neurosci 34:1494–1509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akhondzadeh S, Mojtahedzadeh V, Mirsepassi GR, Moin M, Amini-Nooshabadi H, Kamalipour A (2002) Diazoxide in the treatment of schizophrenia: novel application of potassium channel openers in the treatment of schizophrenia. J Clin Pharm Ther 27:453–459

    Article  CAS  PubMed  Google Scholar 

  • Aller MI, Wisden W (2008) Changes in expression of some two-pore domain potassium channel genes (KCNK) in selected brain regions of developing mice. Neuroscience 151:1154–1172

    Article  CAS  PubMed  Google Scholar 

  • Alloui A, Zimmermann K, Mamet J, Duprat F, Noël J, Chemin J, Guy N, Blondeau N, Voilley N, Rubat-Coudert C, Borsotto M, Romey G, Heurteaux C, Reeh P, Eschalier A, Lazdunski M (2006) TREK-1, a K+ channel involved in polymodal pain perception. EMBO J 25:2368–2376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andres-Bilbe A, Castellanos A, Pujol-Coma A, Callejo G, Comes N, Gasull X (2020) The Background K(+) Channel TRESK in Sensory Physiology and Pain. Int J Mol Sci 21:5206

    Article  CAS  PubMed Central  Google Scholar 

  • Askland K, Read C, O’Connell C, Moore JH (2012) Ion channels and schizophrenia: a gene set-based analytic approach to GWAS data for biological hypothesis testing. Hum Genet 131:373–391

    Article  CAS  PubMed  Google Scholar 

  • Bedoya M, Rinné S, Kiper AK, Decher N, González W, Ramírez D (2019) TASK channels pharmacology: new challenges in drug design. J Med Chem 62:10044–10058

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blin S, Chatelain FC, Feliciangeli S, Kang D, Lesage F, Bichet D (2014) Tandem pore domain halothane-inhibited K+ channel subunits THIK1 and THIK2 assemble and form active channels. J Biol Chem 289:28202–28212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borsotto M, Veyssiere J, Moha Ou Maati H, Devader C, Mazella J, Heurteaux C (2015) Targeting two-pore domain K(+) channels TREK-1 and TASK-3 for the treatment of depression: a new therapeutic concept. Br J Pharmacol 172:771–784

    Article  CAS  PubMed  Google Scholar 

  • Callejo G, Giblin JP, Gasull X (2013) Modulation of TRESK background K+ channel by membrane stretch. PLoS ONE 8:e64471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chavez RA, Gray AT, Zhao BB, Kindler CH, Mazurek MJ, Mehta Y, Forsayeth JR, Yost CS (1999) TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium channel family. J Biol Chem 274:7887–7892

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Talley EM, Patel N, Gomis A, McIntire WE, Dong B, Viana F, Garrison JC, Bayliss DA (2006a) Inhibition of a background potassium channel by Gq protein alpha-subunits. Proc Natl Acad Sci U S A 103:3422–3427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen X, Talley EM, Patel N, Gomis A, McIntire WE, Dong B, Viana F, Garrison JC, Bayliss DA (2006b) Inhibition of a background potassium channel by Gq protein α-subunits. Proc Natl Acad Sci 103:3422–3427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cotten JF (2013) TASK-1 (KCNK3) and TASK-3 (KCNK9) tandem pore potassium channel antagonists stimulate breathing in isoflurane anesthetized rats. Anesth Analg 116:e3182844

    Article  Google Scholar 

  • Czirják G, Petheo GL, Spät As, Enyedi P (2001) Inhibition of TASK-1 potassium channel by phospholipase C. Am J Physiol Cell Physiol 281:C700–C708

    Article  PubMed  Google Scholar 

  • De Franco E, Flanagan SE, Houghton JA, Lango Allen H, Mackay DJ, Temple IK, Ellard S, Hattersley AT (2015) The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study. Lancet 386:957–963

    Article  PubMed  PubMed Central  Google Scholar 

  • Decher N, Maier M, Dittrich W, Gassenhuber J, Brüggemann A, Busch AE, Steinmeyer K (2001) Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family. FEBS Lett 492:84–89

    Article  CAS  PubMed  Google Scholar 

  • Dong YY, Pike AC, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S, Ruda GF, Clausen MV, Cao L, Brennan PE, Burgess-Brown NA, Sansom MS, Tucker SJ, Carpenter EP (2015) K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science 347:1256–1259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dragicevic E, Schiemann J, Liss B (2015) Dopamine midbrain neurons in health and Parkinson’s disease: emerging roles of voltage-gated calcium channels and ATP-sensitive potassium channels. Neuroscience 284:798–814

    Article  CAS  PubMed  Google Scholar 

  • Duprat F, Lesage F, Patel AJ, Fink M, Romey G, Lazdunski M (2000) The neuroprotective agent riluzole activates the two P domain K(+) channels TREK-1 and TRAAK. Mol Pharmacol 57:906–912

    CAS  PubMed  Google Scholar 

  • Enyedi P, Czirják G (2010) Molecular background of leak K+ currents: two-pore domain potassium channels. Physiol Rev 90:559–605

    Article  CAS  PubMed  Google Scholar 

  • Ferrari U, Empl M, Kim KS, Sostak P, Förderreuther S, Straube A (2005) Calcineurin inhibitor-induced headache: clinical characteristics and possible mechanisms. Headache 45:211–214

    Article  PubMed  Google Scholar 

  • Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M (1998) A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J 17:3297–3308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gada K, Plant LD (2019) Two-pore domain potassium channels: emerging targets for novel analgesic drugs: IUPHAR review 26. Br J Pharmacol 176:256–266

    Article  CAS  PubMed  Google Scholar 

  • Gerstin KM, Gong DH, Abdallah M, Winegar BD, Eger EI 2nd, Gray AT (2003) Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change minimum alveolar anesthetic concentration. Anesth Analg 96:1345–1349

    Article  CAS  PubMed  Google Scholar 

  • Girard C, Duprat F, Terrenoire C, Tinel N, Fosset M, Romey G, Lazdunski M, Lesage F (2001) Genomic and functional characteristics of novel human pancreatic 2P domain K+ channels. Biochem Biophys Res Commun 282:249–256

    Article  CAS  PubMed  Google Scholar 

  • Hall AM, Throesch BT, Buckingham SC, Markwardt SJ, Peng Y, Wang Q, Hoffman DA, Roberson ED (2015) Tau-dependent Kv4.2 depletion and dendritic hyperexcitability in a mouse model of Alzheimer’s disease. J Neurosci 35:6221–6230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hervieu GJ, Cluderay JE, Gray CW, Green PJ, Ranson JL, Randall AD, Meadows HJ (2001) Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS. Neuroscience 103:899–919

    Article  CAS  PubMed  Google Scholar 

  • Heurteaux C, Guy N, Laigle C, Blondeau N, Duprat F, Mazzuca M, Lang-Lazdunski L, Widmann C, Zanzouri M, Romey G, Lazdunski M (2004) TREK-1, a K+ channel involved in neuroprotection and general anesthesia. Embo j 23:2684–2695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heurteaux C, Lucas G, Guy N, El Yacoubi M, Thümmler S, Peng XD, Noble F, Blondeau N, Widmann C, Borsotto M, Gobbi G, Vaugeois JM, Debonnel G, Lazdunski M (2006) Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat Neurosci 9:1134–1141

    Article  CAS  PubMed  Google Scholar 

  • Huang H, Li H, Shi K, Wang L, Zhang X, Zhu X (2018) TREK-TRAAK two-pore domain potassium channels protect human retinal pigment epithelium cells from oxidative stress. Int J Mol Med 42:2584–2594

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes S, Foster RG, Peirson SN, Hankins MW (2017) Expression and localisation of two-pore domain (K2P) background leak potassium ion channels in the mouse retina. Sci Rep 7:1–14

    Article  Google Scholar 

  • Humphries ES, Dart C (2015) Neuronal and cardiovascular potassium channels as therapeutic drug targets: promise and pitfalls. J Biomol Screen 20:1055–1073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanda H, Ling J, Tonomura S, Noguchi K, Matalon S, Gu JG (2019) TREK-1 and TRAAK are principal K+ channels at the nodes of ranvier for rapid action potential conduction on mammalian myelinated afferent nerves. Neuron 104:960-971.e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang D, Hogan JO, Kim D (2014) THIK-1 (K2P13.1) is a small-conductance background K(+) channel in rat trigeminal ganglion neurons. Pflugers Arch 466:1289–1300

    Article  CAS  PubMed  Google Scholar 

  • Kasianowicz JJ (2012) Introduction to ion channels and disease. Chem Rev 112:6215–6217

    Article  CAS  PubMed  Google Scholar 

  • Kim D (2005) Physiology and pharmacology of two-pore domain potassium channels. Curr Pharm Des 11:2717–2736

    Article  CAS  PubMed  Google Scholar 

  • Kim D, Cavanaugh EJ, Kim I, Carroll JL (2009) Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells. J Physiol 587:2963–2975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim Y, Gnatenco C, Bang H, Kim D (2001) Localization of TREK-2 K+ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and pHi. Pflugers Arch 442:952–960

    Article  CAS  PubMed  Google Scholar 

  • Kim DS, Kim JE, Kwak SE, Choi HC, Song HK, Kimg YI, Choi SY, Kang TC (2007) Up-regulated astroglial TWIK-related acid-sensitive K+ channel-1 (TASK-1) in the hippocampus of seizure-sensitive gerbils: a target of anti-epileptic drugs. Brain Res 1185:346–358

    Article  CAS  PubMed  Google Scholar 

  • Kindler CH, Yost CS (2005) Two-pore domain potassium channels: new sites of local anesthetic action and toxicity. Reg Anesth Pain Med 30:260–274

    Article  CAS  PubMed  Google Scholar 

  • Kindler CH, Yost SC, Gray AT (1999) Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem. J Am Soc Anesthesiol 90:1092–1102

    Article  CAS  Google Scholar 

  • Lafrenière RG, Rouleau GA (2011) Migraine: role of the TRESK two-pore potassium channel. Int J Biochem Cell Biol 43:1533–1536

    Article  PubMed  Google Scholar 

  • Lafrenière RG, Cader MZ, Poulin J-F, Andres-Enguix I, Simoneau M, Gupta N, Boisvert K, Lafrenière F, McLaughlan S, Dubé M-P (2010) A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura. Nat Med 16:1157–1160

    Article  PubMed  Google Scholar 

  • Lamas JA, Fernández-Fernández D (2019) Tandem pore TWIK-related potassium channels and neuroprotection. Neural Regen Res 14:1293–1308

    Article  PubMed  PubMed Central  Google Scholar 

  • Lazarenko RM, Willcox SC, Shu S, Berg AP, Jevtovic-Todorovic V, Talley EM, Chen X, Bayliss DA (2010) Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics. J Neurosci 30:7691–7704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee A, Smart J, Rubinstein M, Low M, Tse A (2011a) Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes. Endocrinology 152:1901–1910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lengyel M, Czirják G, Jacobson DA, Enyedi P (2020) TRESK and TREK-2 two-pore-domain potassium channel subunits form functional heterodimers in primary somatosensory neurons. J Biol Chem 295:12408–12425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim CX, Ricos MG, Dibbens LM, Heron SE (2016) KCNT1 mutations in seizure disorders: the phenotypic spectrum and functional effects. J Med Genet 53:217–225

    Article  CAS  PubMed  Google Scholar 

  • Lin DH, Zhang XR, Ye DQ, Xi GJ, Hui JJ, Liu SS, Li LJ, Zhang ZJ (2015) The role of the two-pore domain potassium channel TREK-1 in the therapeutic effects of escitalopram in a rat model of poststroke depression. CNS Neurosci Ther 21:504–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linden AM, Sandu C, Aller MI, Vekovischeva OY, Rosenberg PH, Wisden W, Korpi ER (2007) TASK-3 knockout mice exhibit exaggerated nocturnal activity, impairments in cognitive functions, and reduced sensitivity to inhalation anesthetics. J Pharmacol Exp Ther 323:924–934

    Article  CAS  PubMed  Google Scholar 

  • Lindner M, Leitner MG, Halaszovich CR, Hammond GR, Oliver D (2011) Probing the regulation of TASK potassium channels by PI (4, 5) P2 with switchable phosphoinositide phosphatases. J Physiol 589:3149–3162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopes CM, Rohács T, Czirják G, Balla T, Enyedi P, Logothetis DE (2005) PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels. J Physiol 564:117–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lotshaw DP (2007) Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels. Cell Biochem Biophys 47:209–256

    Article  CAS  PubMed  Google Scholar 

  • Maingret F, Patel AJ, Lesage F, Lazdunski M, Honoré E (2000) Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK. J Biol Chem 275:10128–10133

    Article  CAS  PubMed  Google Scholar 

  • Marsh B, Acosta C, Djouhri L, Lawson SN (2012) Leak K+ channel mRNAs in dorsal root ganglia: relation to inflammation and spontaneous pain behaviour. Mol Cell Neurosci 49:375–386

    Article  CAS  PubMed  Google Scholar 

  • Mathie A (2007) Neuronal two-pore-domain potassium channels and their regulation by G protein-coupled receptors. J Physiol 578:377–385

    Article  CAS  PubMed  Google Scholar 

  • Mathie A, Veale E (2007a) Therapeutic potential of neuronal two-pore domain potassium-channel modulators. Curr Opin Invest Drugs 8:555–562

    CAS  Google Scholar 

  • Mathie A, Veale EL (2007b) Therapeutic potential of neuronal two-pore domain potassium-channel modulators. Curr Opin Investig Drugs 8:555–562

    CAS  PubMed  Google Scholar 

  • Meadows HJ, Benham CD, Cairns W, Gloger I, Jennings C, Medhurst AD, Murdock P, Chapman CG (2000) Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel. Pflugers Arch 439:714–722

    Article  CAS  PubMed  Google Scholar 

  • Medhurst AD, Rennie G, Chapman CG, Meadows H, Duckworth MD, Kelsell RE, Gloger II, Pangalos MN (2001) Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Brain Res Mol Brain Res 86:101–114

    Article  CAS  PubMed  Google Scholar 

  • Meuth SG, Aller MI, Munsch T, Schuhmacher T, Seidenbecher T, Meuth P, Kleinschnitz C, Pape HC, Wiendl H, Wisden W, Budde T (2006) The contribution of TWIK-related acid-sensitive K+-containing channels to the function of dorsal lateral geniculate thalamocortical relay neurons. Mol Pharmacol 69:1468–1476

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller AN, Long SB (2012) Crystal structure of the human two-pore domain potassium channel K2P1. Science 335:432–436

    Article  CAS  PubMed  Google Scholar 

  • Nagaraj C, Tang B, Bálint Z, Wygrecka M, Hrzenjak A, Kwapiszewska G, Stacher E, Lindenmann J, Weir EK, Olschewski H (2013) Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries. Eur Respir J 41:85–95

    Article  CAS  PubMed  Google Scholar 

  • Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (eds) (2012) Jasper’s basic mechanisms of the epilepsies. National Center for Biotechnology Information (US) In: Rogawski MA, Delgado-Escueta AV, Noebels JL, Avoli M, Olsen RW Bethesda (MD)

  • Patel AJ, Honoré E, Lesage F, Fink M, Romey G, Lazdunski M (1999) Inhalational anesthetics activate two-pore-domain background K+ channels. Nat Neurosci 2:422–426

    Article  CAS  PubMed  Google Scholar 

  • Patel AJ, Honoré E, Maingret F, Lesage F, Fink M, Duprat F, Lazdunski M (1998) A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J 17:4283–4290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel AJ, Maingret F, Magnone V, Fosset M, Lazdunski M, Honoré E (2000) TWIK-2, an inactivating 2P domain K+ channel. J Biol Chem 275:28722–28730

    Article  CAS  PubMed  Google Scholar 

  • Pereira C, Martins LM, Saraiva L (2014) LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model. Biochim Biophys Acta 1840:2025–2031

    Article  CAS  PubMed  Google Scholar 

  • Putzke C, Hanley PJ, Schlichthorl G, Preisig-Muller R, Rinne S, Anetseder M, Eckenhoff R, Berkowitz C, Vassiliou T, Wulf H (2007a) Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1. Am J Physiol Cell Physiol 293:C1319–C1326

    Article  CAS  PubMed  Google Scholar 

  • Putzke C, Wemhöner K, Sachse FB, Rinné S, Schlichthörl G, Li XT, Jaé L, Eckhardt I, Wischmeyer E, Wulf H (2007b) The acid-sensitive potassium channel TASK-1 in rat cardiac muscle. Cardiovasc Res 75:59–68

    Article  CAS  PubMed  Google Scholar 

  • Rajan S, Wischmeyer E, Karschin C, Preisig-Müller R, Grzeschik K-H, Daut J, Karschin A, Derst C (2001) THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels*210. J Biol Chem 276:7302–7311

    Article  CAS  PubMed  Google Scholar 

  • Renigunta V, Zou X, Kling S, Schlichthörl G, Daut J (2014) Breaking the silence: functional expression of the two-pore-domain potassium channel THIK-2. Pflugers Arch 466:1735–1745

    Article  CAS  PubMed  Google Scholar 

  • Ru Q, Tian X, Wu YX, Wu RH, Pi MS, Li CY (2014) Voltage-gated and ATP-sensitive K+ channels are associated with cell proliferation and tumorigenesis of human glioma. Oncol Rep 31:842–848

    Article  CAS  PubMed  Google Scholar 

  • Schiekel J, Lindner M, Hetzel A, Wemhöner K, Renigunta V, Schlichthörl G, Decher N, Oliver D, Daut J (2013) The inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C. Cardiovasc Res 97:97–105

    Article  CAS  PubMed  Google Scholar 

  • Schroeder BC, Kubisch C, Stein V, Jentsch TJ (1998) Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature 396:687–690

    Article  CAS  PubMed  Google Scholar 

  • Sepúlveda FV, Pablo Cid L, Teulon J, Niemeyer MI (2015) Molecular aspects of structure, gating, and physiology of pH-sensitive background K2P and Kir K+-transport channels. Physiol Rev 95:179–217

    Article  PubMed  PubMed Central  Google Scholar 

  • Seyler C, Duthil-Straub E, Zitron E, Gierten J, Scholz EP, Fink R, Karle C, Becker R, Katus H, Thomas D (2012) TASK1 (K2P3. 1) K+ channel inhibition by endothelin-1 is mediated through Rho kinase-dependent phosphorylation. Br J Pharmacol 165:1467–1475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talley EM, Solorzano G, Lei Q, Kim D, Bayliss DA (2001) Cns distribution of members of the two-pore-domain (KCNK) potassium channel family. J Neurosci 21:7491–7505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thümmler S, Duprat F, Lazdunski M (2007) Antipsychotics inhibit TREK but not TRAAK channels. Biochem Biophys Res Commun 354:284–289

    Article  PubMed  Google Scholar 

  • Tong L, Cai M, Huang Y, Zhang H, Su B, Li Z, Dong H (2014) Activation of K2P channel–TREK1 mediates the neuroprotection induced by sevoflurane preconditioning. British J Anaesth 113:157–167

    Article  CAS  Google Scholar 

  • Veale EL, Buswell R, Clarke CE, Mathie A (2007) Identification of a region in the TASK3 two pore domain potassium channel that is critical for its blockade by methanandamide. Br J Pharmacol 152:778–786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verkest, C, Häfner, S, Ávalos Prado, P, Baron, A, Sandoz, G (2020). Migraine and Two-Pore-Domain Potassium Channels. Neuroscientist. https://doi.org/10.1177/1073858420940949

  • Vukadinovic Z, Rosenzweig I (2012) Abnormalities in thalamic neurophysiology in schizophrenia: could psychosis be a result of potassium channel dysfunction? Neurosci Biobehav Rev 36:960–968

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Zeng J, Ren R, Chen S (2008) Potassium channels in the basal ganglia: promising new targets for the treatment of Parkinson’s disease. Front Biosci 13:3825–3838

    Article  CAS  PubMed  Google Scholar 

  • Wickenden AD (2002) Potassium channels as anti-epileptic drug targets. Neuropharmacology 43:1055–1060

    Article  CAS  PubMed  Google Scholar 

  • Wilke BU, Lindner M, Greifenberg L, Albus A, Kronimus Y, Bünemann M, Leitner MG, Oliver D (2014) Diacylglycerol mediates regulation of TASK potassium channels by Gq-coupled receptors. Nat Commun 5:1–11

    Article  Google Scholar 

  • Wu F, Sun H, Gong W, Li X, Pan Z, Shan H, Zhang Z (2021) Genetic and pharmacological inhibition of two-pore domain potassium channel TREK-1 alters depression-related behaviors and neuronal plasticity in the hippocampus in mice. CNS Neurosci Ther 27:220–232

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Pan Y, Wang X (2004) Alterations in the expression of lipid and mechano-gated two-pore domain potassium channel genes in rat brain following chronic cerebral ischemia. Brain Res Mol Brain Res 120:205–209

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Jan YN, Jan LY (1995) Determination of the subunit stoichiometry of an inwardly rectifying potassium channel. Neuron 15:1441–1447

    Article  CAS  PubMed  Google Scholar 

  • Yeh CY, Bulas AM, Moutal A, Saloman JL, Hartnett KA, Anderson CT, Tzounopoulos T, Sun D, Khanna R, Aizenman E (2017) Targeting a potassium channel/syntaxin interaction ameliorates cell death in ischemic stroke. J Neurosci 37:5648–5658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young CC, Stegen M, Bernard R, Müller M, Bischofberger J, Veh RW, Haas CA, Wolfart J (2009) Upregulation of inward rectifier K+ (Kir2) channels in dentate gyrus granule cells in temporal lobe epilepsy. J Physiol 587:4213–4233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoo S, Liu J, Sabbadini M, Au P, Xie G-x, Yost CS (2009) Regional expression of the anesthetic-activated potassium channel TRESK in the rat nervous system. Neurosci Lett 465:79–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yost CS (2003) Update on tandem pore (2P) domain K+ channels. Curr Drug Targets 4:347–351

    Article  CAS  PubMed  Google Scholar 

  • Yost CS, Oh I, Eger EI, Sonner JM (2008) Knockout of the gene encoding the K2P channel KCNK7 does not alter volatile anesthetic sensitivity. Behav Brain Res 193:192–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Kim EC, Chen C, Procko E, Pant S, Lam K, Patel J, Choi R, Hong M, Joshi D (2020) Identifying mutation hotspots reveals pathogenetic mechanisms of KCNQ2 epileptic encephalopathy. Sci Rep 10:1–19

    Google Scholar 

  • Zhang L, Li X, Zhou R, Xing G (2006) Possible role of potassium channel, big K in etiology of schizophrenia. Med Hypotheses 67:41–43

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Author is thankful to the department of Pharmaceuticals, Ministry of Chemical and Fertilizers, Govt. of India, for providing necessary support to carry out this study.

Funding

No Funding has been received for this work.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Export Promotions Industrial Park (EPIP), Industrial Area, Hajipur, District, Vaishali, 844102, Bihar, India

    Punita Aggarwal, Sanjiv Singh & V. Ravichandiran

Authors
  1. Punita Aggarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanjiv Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Ravichandiran
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

VR and PA designed the research. SS wrote the manuscript. All authors read and edited the manuscript.

Corresponding author

Correspondence to Sanjiv Singh.

Ethics declarations

Conflict of interest

The authors declare no competing financial interest.

Ethical Approval

No animal or human study done in this work.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised: In this article, the order that the authors appeared in the author list was incorrect. Also, the author name ‘Punita Aggarwal’ was incorrectly written as ‘Punita Agarwal’.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aggarwal, P., Singh, S. & Ravichandiran, V. Two-Pore Domain Potassium Channel in Neurological Disorders. J Membrane Biol 254, 367–380 (2021). https://doi.org/10.1007/s00232-021-00189-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-021-00189-8

Keywords

Search

Navigation