Skip to main content

Potassium and Mitochondria

  • Chapter
  • First Online:
  • 1117 Accesses

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Mitochondria have been recognized for their multifunctional roles in energy transduction, ion transport, signaling, and cell death. Mitochondrial dysfunctions lead to various neurodegenerative disorders and mitochondrial diseases, including Parkinson’s disease, Alzheimer’s disease, and brain/spinal cord ischemia. It has been observed that potassium flux through the inner mitochondrial membrane regulates the concentration of reactive oxygen species, affects the mitochondrial volume, and changes both the mitochondrial membrane potential and the transport of calcium into the mitochondria. In recent years, a number of potassium channels present in the inner mitochondrial membrane have been described. These findings include an ATP-regulated potassium channel, a large-conductance Ca2+-regulated potassium channel, an intermediate-conductance Ca2+-regulated potassium channel, a voltage-gated potassium channel, and a twin-pore domain potassium channel. However, our understanding of the structure of mitochondrial potassium channels is still limited. Additionally, it has been shown that activation of mitochondrial potassium channels protects against both necrotic and apoptotic cell death during myocardial infarction or cerebral hypoxia. These results stimulated an intensive study of the pharmacology of mitochondrial potassium channels and contributed to the development of many hypotheses concerning the role of potassium influx to the mitochondrial matrix in cell death.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Ardehali H, Chen Z, Ko Y, Mejia-Alvarez R, Marban E (2004) Multiprotein complex containing succinate dehydrogenase confers mitchondrial ATP-sensitive K+ channel activity. Proc Natl Acad Sci USA 101:11880–11885

    Article  PubMed  CAS  Google Scholar 

  • Bajgar R, Seetharaman S, Kowaltowski AJ, Garlid KD, Paucek P (2001) Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain. J Biol Chem 276:33369–33374

    Article  PubMed  CAS  Google Scholar 

  • Bednarczyk P, Kicińska A, Kominkova V, Ondrias K, Dołowy K, Szewczyk A (2004) Quinine inhibits mitochondrial ATP-regulated potassium channel from bovine heart. J Membr Biol 199:63–72

    Article  PubMed  CAS  Google Scholar 

  • Bednarczyk P, Dołowy K, Szewczyk A (2005) Matrix Mg2+ regulates mitochondrial ATP-dependent potassium channel from heart. FEBS Lett 579:1625–1632

    Article  PubMed  CAS  Google Scholar 

  • Bednarczyk P, Dołowy K, Szewczyk A (2008) New properties of mitochondrial ATP-regulated potassium channels. J Bioenerg Biomembr 40:325–335

    Article  PubMed  CAS  Google Scholar 

  • Bednarczyk P, Kowalczyk JE, Beresewicz M, Dołowy K, Szewczyk A, Zabłocka B (2010) Identification of a voltage-gated potassium channel in gerbil hippocampal mitochondria. Biochem Biophys Res Commun 397:614–620

    Article  PubMed  CAS  Google Scholar 

  • Bernardi P (1999) Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev 79:1127–1155

    PubMed  CAS  Google Scholar 

  • Bittner S, Budde T, Wiendl H, Meuth SG (2010) From the background to the spotlight: TASK channels in pathological conditions. Brain Pathol 20:999–1009

    Article  PubMed  CAS  Google Scholar 

  • Busija DW, Gaspar T, Domoki F, Katakam PV, Bari F (2008) Mitochondrial-mediated suppression of ROS production upon exposure of neurons to lethal stress: mitochondrial targeted preconditioning. Adv Drug Deliv Rev 60:1471–1417

    Article  PubMed  CAS  Google Scholar 

  • Cancherini DV, Trabuco LG, Reboucas NA, Kowaltowski AJ (2003) ATP-sensitive K+ channels in renal mitochondria. Am J Physiol Renal Physiol 285:F1291–F1296

    PubMed  CAS  Google Scholar 

  • Chandy KG, Wulff H, Beeton C, Pennington M, Gutman GA, Cahalan MD (2004) K+ channels as targets for specific immunomodulation. Trends Pharmacol Sci 25:280–289

    Article  PubMed  CAS  Google Scholar 

  • Cheng Y, Gu XQ, Bednarczyk P, Wiedemann FR, Haddad GG, Siemen D (2008) Hypoxia increases activity of the BK-channel in the inner mitochondrial membrane and reduces activity of the permeability transition pore. Cell Physiol Biochem 22:127–136

    Article  PubMed  CAS  Google Scholar 

  • Chiandussi E, Petrussa E, Macrì F, Vianello A (2002) Modulation of a plant mitochondrial K+ ATP channel and its involvement in cytochrome c release. J Bioenerg Biomembr 34:177–184

    Article  PubMed  CAS  Google Scholar 

  • Choma K, Bednarczyk P, Koszela-Piotrowska I, Kulawiak B, Kudin A, Kunz WS, Dołowy K, Szewczyk A (2009) Single channel studies of the ATP-regulated potassium channel in brain mitochondria. J Bioenerg Biomembr 41:323–334

    Article  PubMed  CAS  Google Scholar 

  • Dahlem YA, Horn TF, Buntinas L, Gonoi T, Wolf G, Siemen D (2004) The human mitochondrial KATP channel is modulated by calcium and nitric oxide: a patch-clamp approach. Biochim Biophys Acta 1656:46–56

    Article  PubMed  CAS  Google Scholar 

  • De Marchi U, Sassi N, Fioretti B, Catacuzzeno L, Cereghetti GM, Szabò I, Zoratti M (2009) Intermediate conductance Ca2+-activated potassium channel (KCa3.1) in the inner mitochondrial membrane of human colon cancer cells. Cell Calcium 45:509–516

    Article  PubMed  Google Scholar 

  • Dębska G, May R, Kicińska A, Szewczyk A, Elger CE, Kunz WS (2001) Potassium channel openers depolarize hippocampal mitochondria. Brain Res 892:42–50

    Article  PubMed  Google Scholar 

  • Dębska G, Kicińska A, Skalska J, Szewczyk A, May R, Elger CE, Kunz WS (2002) Opening of potassium channels modulates mitochondrial function in rat skeletal muscle. Biochim Biophys Acta 1556:97–105

    Article  PubMed  Google Scholar 

  • Edwards JC, Kahl CR (2010) Chloride channels of intracellular membranes. FEBS Lett 584:2102–2111

    Article  PubMed  CAS  Google Scholar 

  • Fernández-Salas E, Sagar M, Cheng C, Yuspa SH, Weinberg WC (1999) p53 and tumor necrosis factor alpha regulate the expression of a mitochondrial chloride channel protein. J Biol Chem 274:36488–36497

    Article  PubMed  Google Scholar 

  • Garlid KD, Paucek P (2003) Mitochondrial potassium transport: the K+ cycle. Biochim Biophys Acta 1606:23–41

    Article  PubMed  CAS  Google Scholar 

  • Gaspar T, Snipes JA, Busija AR, Kis B, Domoki F, Bari F, Busija DW (2008) ROS-independent preconditioning in neurons via activation of mitoKATP channels by BMS-191095. J Cereb Blood Flow Metab 28:1090–1103

    Article  PubMed  CAS  Google Scholar 

  • Ghatta S, Nimmagadda D, Xu X, O’Rourke ST (2006) Large-conductance, calcium-activated potassium channels: structural and functional implications. Pharmacol Ther 110:103–116

    Article  PubMed  CAS  Google Scholar 

  • Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629

    Article  PubMed  CAS  Google Scholar 

  • Grunnet M, Rasmussen HB, Hay-Schmidt A, Klaerke DA (2003) The voltage-gated potassium channel subunit, Kv1.3, is expressed in epithelia. Biochim Biophys Acta 1616:85–94

    Article  PubMed  CAS  Google Scholar 

  • Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol Rev 57:473–508

    Article  PubMed  CAS  Google Scholar 

  • Hamanaka RB, Chandel NS (2010) Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35:505–513

    Article  PubMed  CAS  Google Scholar 

  • Hanley PJ, Daut JK (2005) KATP channels and preconditioning: a re-examination of the role of mitochondrial KATP channels and an overview of alternative mechanisms. J Mol Cell Cardiol 39:17–50

    Article  PubMed  CAS  Google Scholar 

  • Inoue I, Nagase H, Kishi K, Higuti T (1991) ATP-sensitive K+ channel in the mitochondrial inner membrane. Nature 352:244–247

    Article  PubMed  CAS  Google Scholar 

  • Kicińska A, Świda A, Bednarczyk P, Koszela-Piotrowska I, Choma K, Dołowy K, Szewczyk A, Jarmuszkiewicz W (2007) ATP-sensitive potassium channel in mitochondria of the eukaryotic microorganism, Acanthamoeba castellanii. J Biol Chem 282:17433–17441

    Article  PubMed  Google Scholar 

  • Koszela-Piotrowska I, Matkovic K, Szewczyk A, Jarmuszkiewicz W (2009) A large-conductance calcium-activated potassium channel in potato (Solanum tuberosum) tuber mitochondria. Biochem J 424:307–316

    Article  PubMed  CAS  Google Scholar 

  • Kulawiak B, Bednarczyk P (2005) Reconstitution of brain mitochondria inner membrane into planar lipid bilayer. Acta Neurobiol Exp 65:271–276

    Google Scholar 

  • Lacza Z, Snipes JA, Kis B, Szabo C, Grover G, Busija DW (2003) Investigation of the subunit composition and the pharmacology of the mitochondrial ATP-dependent K+ channel in the brain. Brain Res 994:27–36

    Article  PubMed  CAS  Google Scholar 

  • Lesage F, Lazdunski M (2000) Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol 279:F793–F801

    CAS  Google Scholar 

  • Matkovic K, Koszela-Piotrowska I, Jarmuszkiewicz W, Szewczyk A (2011) Ion conductance pathways in potato tuber (Solanum tuberosum) inner mitochondrial membrane. Biochim Biophys Acta 1807:275–285

    Article  PubMed  CAS  Google Scholar 

  • Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biol Rev Camb Phil Soc 41:445–502

    Article  CAS  Google Scholar 

  • Mourre C, Chernova MN, Martin-Eauclaire MF, Bessone R, Jacquet G, Gola M, Alper SL, Crest M (1999) Distribution in rat brain of binding sites of kaliotoxin, a blocker of Kv1.1 and Kv1.3 alpha-subunits. J Pharmacol Exp Ther 291:943–52

    PubMed  CAS  Google Scholar 

  • Nakae Y, Kwok WM, Bosnjak ZJ, Jiang MT (2003) Isoflurane activates rat mitochondrial ATP-sensitive K+ channels reconstituted in lipid bilayers. Am J Physiol 284:H1865–H1871

    CAS  Google Scholar 

  • Nicholls DG (2005) Mitochondria and calcium signaling. Cell Calcium 38:311–317

    Article  PubMed  CAS  Google Scholar 

  • Nicholls DG, Ferguson SJ (2002) Bioenergetics 3. Academic Press, London

    Google Scholar 

  • Nowikovsky K, Schweyen RJ, Bernardi P (2009) Pathophysiology of mitochondrial volume homeostasis: potassium transport and permeability transition. Biochim Biophys Acta 787:345–350

    Google Scholar 

  • Paucek P, Mironova G, Mahdi F, Beavis AD, Woldegiorgis G, Garlid KD (1992) Reconstitution and partial purification of the glibenclamide-sensitive, ATP-dependent K+ channel from rat liver and beef heart mitochondria. J Biol Chem 267:26062–26069

    PubMed  CAS  Google Scholar 

  • Piwońska M, Wilczek E, Szewczyk A, Wilczyński GM (2008) Differential distribution of Ca2+-activated potassium channel β4 subunit in rat brain: immunolocalization in neuronal mitochondria. Neuroscience 153:446–460

    Article  PubMed  Google Scholar 

  • Rusznak Z, Bakondi G, Kosztka L, Pocsai K, Diens B, Fodor J, Telek A, Gomczi M, Szucs G, Csernoch L (2008) Mitochondrial expression of the two-pore domain TASK-3 channels in malignantly transformed and non-malignant human cells. Virchows Arch 452:415–426

    Article  PubMed  CAS  Google Scholar 

  • Sassi N, De Marchi U, Fioretti B, Biasutto L, Gulbins E, Franciolini F, Szabò I, Zoratti M (2010) An investigation of the occurrence and properties of the mitochondrial intermediate-conductance Ca2+-activated K+ channel mtKCa3.1. Biochim Biophys Acta 1797:1260–1267

    Article  PubMed  CAS  Google Scholar 

  • Sato T, Saito T, Saegusa N, Nakaya H (2005) Mitochondrial Ca2+-activated K+ channels in cardiac myocytes: a mechanism of the cardioprotective effect and modulation by protein kinase A. Circulation 111:198–203

    Article  PubMed  CAS  Google Scholar 

  • Siemen D, Loupatatzis C, Borecky J, Gulbins E, Lang F (1999) Ca2+-activated K channel of the BK-type in the inner mitochondrial membrane of a human glioma cell line. Biochem Biophys Res Commun 257:549–554

    Article  PubMed  CAS  Google Scholar 

  • Skalska J, Piwońska M, Wyroba E, Surmacz L, Wieczorek R, Koszela-Piotrowska I, Zielińska J, Bednarczyk P, Dołowy K, Wilczyński GM, Szewczyk A, Kunz WS (2008) A novel potassium channel in skeletal muscle mitochondria. Biochim Biophys Acta 1777:651–659

    Article  PubMed  CAS  Google Scholar 

  • Skalska J, Bednarczyk P, Piwońska M, Kulawiak B, Wilczyński G, Dołowy K, Kudin AP, Kunz WS, Szewczyk A (2009) Calcium ions regulate K uptake into brain mitochondria: the evidence for a novel potassium channel. Int J Mol Sci 10:1104–1120

    Article  PubMed  CAS  Google Scholar 

  • Szabo I, Bock J, Jekle A, Soddemann M, Adams C, Lang F, Zoratti M, Gulbins E (2005) A novel potassium channel in lymphocyte mitochondria. J Biol Chem 280:12790–12798

    Article  PubMed  CAS  Google Scholar 

  • Szabo I, Bock J, Grassmé H, Soddemann M, Wilker B, Lang F, Zoratti M, Gulbins E (2008) Mitochondrial potassium channel Kv1.3 mediates Bax-induced apoptosis in lymphocytes. Proc Natl Acad Sci USA 105:14861–14866

    Article  PubMed  CAS  Google Scholar 

  • Szewczyk A, Wojtczak L (2002) Mitochondria as a pharmacological target. Pharmacol Rev 54:104–127

    Article  Google Scholar 

  • Szewczyk A, Jarmuszkiewicz W, Kunz WS (2009) Mitochondrial potassium channels. IUBMB Life 61:134–143

    Article  PubMed  CAS  Google Scholar 

  • Szewczyk A, Kajma A, Malińska D, Wrzosek A, Bednarczyk P, Zabłocka B, Dołowy K (2010) Pharmacology of mitochondrial potassium channels: dark side of the field. FEBS Lett 584:2063–2069

    Article  PubMed  CAS  Google Scholar 

  • Watanabe M, Katsura K, Ohsawa I, Mizukoshi G, Takahashi K, Asoh S, Ohta S, Katayama Y (2008) Involvement of mitoKATP channel in protective mechanisms of cerebral ischemic tolerance. Brain Res 1238:199–207

    Article  PubMed  CAS  Google Scholar 

  • Wegener S, Gottschalk B, Jovanovic V, Knab R, Fiebach JB, Schellinger PD, Kucinski T, Jungehülsing GJ, Brunecker P, Müller B, Banasik A, Amberger N, Wernecke KD, Siebler M, Röther J, Villringer A, Weih M, MRI in Acute Stroke Study Group of the German Competence Network Stroke (2004) Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study. Stroke 35:616–621

    Article  PubMed  Google Scholar 

  • Xu W, Liu Y, Wang S, McDonald T, Van Eyk JE, Sidor A, O’Rourke B (2002) Cytoprotective role of Ca2+-activated K+ channels in the cardiac inner mitochondrial membrane. Science 298:1029–1033

    Article  PubMed  CAS  Google Scholar 

  • Yao X, Chang AY, Boulpaep EL, Segal AS, Desir GV (1996) Molecular cloning of a glibenclamide-sensitive, voltage-gated potassium channel expressed in rabbit kidney. J Clin Invest 97:2525–2533

    Article  PubMed  CAS  Google Scholar 

  • Zhang DX, Chen YF, Campbell WB, Zou AP, Gross GJ, Li PL (2001) Characteristics and superoxide-induced activation of reconstituted myocardial mitochondrial ATP-sensitive potassium channels. Circ Res 89:1177–1183

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I wish to thank Prof. Adam Szewczyk and Prof. Krzysztof Dołowy for introducing me to the study of mitochondrial channels and for stimulating discussions. This chapter was supported by the Polish Mitochondrial Network (MitoNet.pl) and the Ministry of Science and Higher Education grant No. 1828/B/P01/2010/39.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Piotr Bednarczyk .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bednarczyk, P. (2012). Potassium and Mitochondria. In: Li, Y., Zhang, J. (eds) Metal Ion in Stroke. Springer Series in Translational Stroke Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9663-3_18

Download citation

Publish with us

Policies and ethics