title: Characterization of distinct single-channel properties of Ca²⁺ inward currents in mitochondria.
abstract: Previous studies have demonstrated several molecularly distinct players involved in mitochondrial Ca(2+) uptake. In the present study, electrophysiological recordings on mitoplasts that were isolated from HeLa cells were performed in order to biophysically and pharmacologically characterize Ca(2+) currents across the inner mitochondrial membrane. In mitoplast-attached configuration with 105 mM Ca(2+) as a charge carrier, three distinct channel conductances of 11, 23, and 80 pS were observed. All types of mitochondrial currents were voltage-dependent and essentially depended on the presence of Ca(2+) in the pipette. The 23 pS channel exhibited burst kinetics. Though all channels were sensitive to ruthenium red, their sensitivity was different. The 11 and 23 pS channels exhibited a lower sensitivity to ruthenium red than the 80 pS channel. The activities of all channels persisted in the presence of cylosporin A, CGP 37187, various K(+)-channel inhibitors, and Cl(-) channel blockers disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate and niflumic acid. Collectively, our data identified multiple conductances of Ca(2+) currents in mitoplasts isolated from HeLa cells, thus challenging the dogma of only one unique mitochondrial Ca(2+) uniporter.
authors: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/III, 8010 Graz, Austria.
authors: Alexander I
authors: AI
authors: Bondarenko
authors: Claire
authors: C
authors: Jean-Quartier
authors: Roland
authors: R
authors: Malli
authors: Wolfgang F
authors: WF
authors: Graier
mesh_terms: D000200:Action Potentials; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D051336:Mitochondrial Membranes / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D026902:Potassium Channel Blockers; D012430:Ruthenium Red; D016572:Cyclosporine; D002118:Calcium
references: Sci China Life Sci. 2011 Aug;54(8):763-9
references: 21786199
references: FEBS Lett. 2010 May 17;584(10):2085-92
references: 20100478
references: Nature. 2010 Sep 16;467(7313):291-6
references: 20693986
references: Circulation. 2009 May 12;119(18):2435-43
references: 19398664
references: FEBS Lett. 2010 May 17;584(10):1948-55
references: 20096690
references: Science. 2009 Oct 2;326(5949):144-7
references: 19797662
references: FEBS Lett. 2010 May 17;584(10):1942-7
references: 20074570
references: J Biol Chem. 2011 Aug 12;286(32):28444-55
references: 21613221
references: Am J Physiol Gastrointest Liver Physiol. 2003 Aug;285(2):G274-81
references: 12851217
references: Nature. 2011 Jun 19;476(7360):341-5
references: 21685886
references: J Biol Chem. 2003 May 9;278(19):17190-7
references: 12598526
references: J Biol Chem. 2011 Jun 17;286(24):21324-9
references: 21524998
references: Cell Calcium. 2000 Nov-Dec;28(5-6):339-48
references: 11115373
references: Nature. 2008 Dec 4;456(7222):605-10
references: 19052620
references: Nature. 2004 Jan 22;427(6972):360-4
references: 14737170
references: J Biol Chem. 1992 Feb 15;267(5):2934-9
references: 1737749
references: Cell. 2008 Dec 26;135(7):1165-7
references: 19109886
references: Cell Calcium. 2010 May;47(5):433-40
references: 20403634
references: Mol Cell Endocrinol. 2012 Apr 28;353(1-2):114-27
references: 22100614
references: Nature. 2011 Jun 19;476(7360):336-40
references: 21685888
references: Pflugers Arch. 2007 Dec;455(3):375-96
references: 17611770
references: Cell. 2012 Oct 26;151(3):630-44
references: 23101630
references: Pflugers Arch. 2003 Jun;446(3):309-13
references: 12698369
references: Cell Calcium. 2010 Nov;48(5):288-301
references: 21047682
references: Nat Protoc. 2007;2(2):287-95
references: 17406588
references: Nat Cell Biol. 2007 Apr;9(4):445-452
references: 17351641
references: Cardiovasc Res. 2006 Sep 1;71(4):715-24
references: 16860295
references: Curr Pharm Des. 2006;12(18):2249-70
references: 16787253