title: Mitochondria are the main ATP source for a cytosolic pool controlling the activity of ATP-sensitive K(+) channels in mouse cardiac myocytes.
abstract: OBJECTIVE
  The aim was to identify the major ATP source controlling the activity of sarcolemmal K(ATP) channels in ventricular cardiomyocytes.
  
  
  METHODS
  K(ATP)-channel current (I(KATP)) was measured with the patch-clamp technique in either the whole-cell (glycogenolysis blocked by 10 mmol/l EGTA), cell-attached, or inside-out configuration.
  
  
  RESULTS
  In the absence of any substrate, I(KATP) (amplitude 31+/-4 nA; n=5) appeared spontaneously 520+/-160 s (n=6) after whole-cell access. This latency was shortened by exposure to anoxia (117+/-33 s, n=32) and even more by uncoupling (1-10 micromol/l FCCP; 25+/-3 s; n=13) while the amplitude was unchanged. During metabolic inhibition the latency was remarkably prolonged when the F1F0-ATPase was blocked by oligomycin, suggesting that under those conditions the F1F0-ATPase is the major ATP consumer. Glucose (5.5-20.0 mmol/l) in the bath solution did not affect the amplitude of I(KATP) but prolonged its latency compared to respective substrate-free conditions. However, I(KATP) was blocked immediately by mitochondrial substrates. FCCP also induced large I(KATP) in cell-attached measurements in either the absence or presence of glucose and oligomycin.
  
  
  CONCLUSIONS
  The activity of K(ATP) channels in cardiomyocytes of mice is controlled by a cytosolic [ATP] pool for which oxidative phosphorylation is the predominant ATP source.
authors.affiliation: Institut für Physiologie, Abt. Herz-Kreislauf-Physiologie, Friedrich-Schiller-Universität Jena, D-07740, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Knopp
authors.forename: S
authors.initials: S
authors.lastname: Thierfelder
authors.forename: B
authors.initials: B
authors.lastname: Doepner
authors.forename: K
authors.initials: K
authors.lastname: Benndorf
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006352:Heart Ventricles; D000860:Hypoxia / Q000378:metabolism*; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D019289:Pyruvic Acid / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D009840:Oligomycins; D015221:Potassium Channels; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D004533:Egtazic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D006180:Proton-Translocating ATPases; D005947:Glucose