title: Role of the sarcolemmal adenosine triphosphate-sensitive potassium channel in hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility.
abstract: BACKGROUND
  Hyperkalemic cardioplegia (Plegisol) has been shown to result in myocyte swelling and reduced contractility. We have demonstrated the elimination of these detrimental effects by the addition of an adenosine triphosphate-sensitive K+ (KATP) channel opener. To examine whether the mitochondrial or sarcolemmal KATP channel might be involved, volume and contractility in isolated myocytes from wild-type mice and mice lacking the sarcolemmal KATP channel (Kir6.2-/-) were evaluated.
  
  
  METHODS
  Myocytes were perfused for 20 minutes each with control 37 degrees C Tyrode's solution, test solution, and then control solution. Test solutions were (n = 10 per group) either 9 degrees C Plegisol or 9 degrees C Plegisol with 100 micromol/L of diazoxide, a putative mitochondrial-specific KATP channel opener. Cell volume and contractility were measured by digital video microscopy at baseline and during the test solution and reexposure periods.
  
  
  RESULTS
  Myocytes from wild-type mice, perfused with 9 degrees C Plegisol, demonstrated significant cell swelling (11.2% +/- 0.4%; p < 0.01) and diminished contractility (32.5% +/- 9.6% reduction in percent shortening, 47.2% +/- 10.1% reduction in peak velocity of shortening, and 52.0% +/- 8.8% reduction in peak velocity of relengthening; p < 0.05) versus baseline. Cell swelling and diminished contractility were significantly reduced by the addition of diazoxide. In Kir6.2-/- myocytes, Plegisol caused a greatly reduced level of cell swelling (3.2% +/- 0.1%; p < 0.01), and this was unaffected by diazoxide. Contractility was unchanged in Kir6.2-/- myocytes after Plegisol.
  
  
  CONCLUSIONS
  The sarcolemmal KATP channel appears necessary for exaggerated cell swelling and reduced contractility to occur after hyperkalemic cardioplegia in mouse myocytes.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Sandip M
authors.initials: SM
authors.lastname: Prasad
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Al-Dadah
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Byrd
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Flagg
authors.forename: Jefferson
authors.initials: J
authors.lastname: Gomes
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Damiano
authors.forename: Colin G
authors.initials: CG
authors.lastname: Nichols
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lawton
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology / Q000633:toxicity; D002122:Calcium Chloride / Q000494:pharmacology / Q000633:toxicity; D002314:Cardioplegic Solutions / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D048429:Cell Size / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology*; D005260:Female; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D009997:Osmotic Pressure; D011188:Potassium / Q000494:pharmacology / Q000633:toxicity*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology / Q000633:toxicity; D012508:Sarcolemma / Q000201:enzymology*; D012965:Sodium Chloride / Q000494:pharmacology / Q000633:toxicity; D000099161:Kcnj11 Channel
chemical_list: D001639:Bicarbonates; D002122:Calcium Chloride; D002314:Cardioplegic Solutions; D003981:Diazoxide; D007552:Isotonic Solutions; D008274:Magnesium; D011188:Potassium; D024661:Potassium Channels, Inwardly Rectifying; D011189:Potassium Chloride; D012965:Sodium Chloride; D000099161:Kcnj11 Channel; C041711:St. Thomas' Hospital cardioplegic solution; C037692:Tyrode's solution