title: By Regulating Mitochondrial Ca2+-Uptake UCP2 Modulates Intracellular Ca2+.
abstract: BACKGROUND
  The possible role of UCP2 in modulating mitochondrial Ca2+-uptake (mCa2+-uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial.
  
  
  METHODS
  Thus, we analyzed mCa2+-uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca2+-transients from mitochondrial ((Ca2+)m) and intracellular compartment ((Ca2+)c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2-/- mice.
  
  
  RESULTS
  Isolated mitochondria showed a Ru360 sensitive mCa2+-uptake, which was significantly decreased in UCP2-/- (229.4±30.8 FU vs. 146.3±23.4 FU, P<0.05). Single-channel registrations confirmed a Ru360 sensitive voltage-gated Ca2+-channel in mitoplasts, i.e. mCa1, showing a reduced single-channel activity in UCP2-/- (Po,total: 0.34±0.05% vs. 0.07±0.01%, P<0.05). In UCP2-/- cardiomyocytes (Ca2+)m was decreased (0.050±0.009 FU vs. 0.021±0.005 FU, P<0.05) while (Ca2+)c was unchanged (0.032±0.002 FU vs. 0.028±0.004 FU, P>0.05) and transsarcolemmal Ca2+-influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa2+-uptake in WT mitoplasts and (Ca2+)m of cardiomyocytes leading to an increase of (Ca2+)c while no ATP dependent effect was observed in UCP2-/-.
  
  
  CONCLUSIONS
  Our results indicate regulatory effects of UCP2 on mCa2+-uptake. Furthermore, we propose, that previously described inhibitory effects on MCU by ATP may be mediated via UCP2 resulting in changes of excitation contraction coupling.
authors: Department of Internal Medicine II, Paracelsus Medical University, Salzburg, Austria.
authors: Lukas Jaroslaw
authors: LJ
authors: Motloch
authors: Department of Internal Medicine II, Paracelsus Medical University, Salzburg, Austria.|Division of Electrophysiology, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.
authors: Robert
authors: R
authors: Larbig
authors: Department of Internal Medicine II, Paracelsus Medical University, Salzburg, Austria.
authors: Tina
authors: T
authors: Gebing
authors: Department of Internal Medicine II, Paracelsus Medical University, Salzburg, Austria.
authors: Sara
authors: S
authors: Reda
authors: Department of Internal Medicine II, Paracelsus Medical University, Salzburg, Austria.
authors: Astrid
authors: A
authors: Schwaiger
authors: Department of Internal Medicine II, Paracelsus Medical University, Salzburg, Austria.
authors: Johannes
authors: J
authors: Leitner
authors: Department of Internal Medicine II, Paracelsus Medical University, Salzburg, Austria.
authors: Martin
authors: M
authors: Wolny
authors: Division of Electrophysiology, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.
authors: Lars
authors: L
authors: Eckardt
authors: Department of Internal Medicine II, Paracelsus Medical University, Salzburg, Austria.
authors: Uta C
authors: UC
authors: Hoppe
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008817:Mice, Mutant Strains; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017975:Ruthenium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D024101:Mitochondrial Proteins; C112020:Ru 360; D017975:Ruthenium Compounds; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D000255:Adenosine Triphosphate; D002118:Calcium