title: Relationship between mitochondrial matrix volume and cellular volume in response to stress and the role of ATP-sensitive potassium channel.
abstract: BACKGROUND
  Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, this study examined the effect of DZX on mitochondrial volume.
  
  
  RESULTS
  Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG)±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI) ± DZX ± 5-hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in significant mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted in significant mitochondrial swelling compared with baseline volume. The addition of DZX did not alter the response of mitochondrial volume to CPG (P=0.912) but increased swelling in response to MI (P=0.036). The addition of 5-hydroxydecanoate to MI + DZX or CPG+DZX significantly reduced mitochondrial swelling (P<0.003 MI+DZX versus MI + DZX + 5HD; P<0.001 CPG+DZX versus CPG + DZX + 5HD).
  
  
  CONCLUSIONS
  Both cellular and mitochondrial volume increased during exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG; however, it was associated with an increase in mitochondrial volume during MI. 5-Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel in the mechanism of cardioprotection by DZX.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery (M.M.A., E.M.K., C.M.M., A.D.K., R.B.S., J.S.L.) and Departments of Cell Biology and Physiology (H.Z., C.G.N.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Anastacio
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Kanter
authors.forename: Carol M
authors.initials: CM
authors.lastname: Makepeace
authors.forename: Angela D
authors.initials: AD
authors.lastname: Keith
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhang
authors.forename: Richard B
authors.initials: RB
authors.lastname: Schuessler
authors.forename: Colin G
authors.initials: CG
authors.lastname: Nichols
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lawton
mesh_terms: D000818:Animals; D048429:Cell Size / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D054086:KATP Channels / Q000819:agonists / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D053142:Mitochondrial Size / Q000187:drug effects / Q000502:physiology*; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
chemical_list: D054086:KATP Channels; D003981:Diazoxide
keywords: cardioplegia; myocardial ischemia; myocardial stunning; myocytes, cardiac; potassium channels
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