title: Improvement of the metabolic status recovers cardiac potassium channel synthesis in experimental diabetes.
abstract: OBJECTIVE
  The fast transient outward current, I(to,fast) , is the most extensively studied cardiac K(+)  current in diabetic animals. Two hypotheses have been proposed to explain how type-1 diabetes reduces this current in cardiac muscle. The first one is a deficiency in channel expression due to a defect in the trophic effect of insulin. The second one proposes flawed glucose metabolism as the cause of the reduced I(to,fast) . Moreover, little information exists about the effects and possible mechanisms of diabetes on the other repolarizing currents of the human heart: I(to,slow) , I(Kr) , I(Ks) , I(Kur) , I(Kslow)  and I(K1) .
  
  
  METHODS
  We recorded cardiac action potentials and K(+)  currents in ventricular cells isolated from control and streptozotocin- or alloxan-induced diabetic mice and rabbits. Channel protein expression was determined by immunofluorescence.
  
  
  RESULTS
  Diabetes reduces the amplitude of I(to,fast) , I(to,slow)  and I(Kslow) , in ventricular myocytes from mouse and rabbit, with no effect on I(ss) , I(Kr)  or I(K1) . The absence of changes in the biophysical properties of the currents and the immunofluorescence experiments confirmed the reduction in channel protein synthesis. Six-hour incubation of myocytes with insulin or pyruvate recovered current amplitudes and fluorescent staining. The activation of AMP-K reduced the same K(+)  currents in healthy myocytes and prevented the pyruvate-induced current recovery.
  
  
  CONCLUSIONS
  Diabetes reduces K(+)  current densities in ventricular myocytes due to a defect in channel protein synthesis. Activation of AMP-K secondary to deterioration in the metabolic status of the cells is responsible for K(+)  channel reductions.
authors.affiliation: Unidad de Investigación Carlos Médez del Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, México.
authors.forename: J
authors.initials: J
authors.lastname: Torres-Jacome
authors.forename: M
authors.initials: M
authors.lastname: Gallego
authors.forename: J M
authors.initials: JM
authors.lastname: Rodríguez-Robledo
authors.forename: J A
authors.initials: JA
authors.lastname: Sanchez-Chapula
authors.forename: O
authors.initials: O
authors.lastname: Casis
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000200:Action Potentials; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects*; D019289:Pyruvic Acid / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D015221:Potassium Channels; D019289:Pyruvic Acid; D055372:AMP-Activated Protein Kinases; D011188:Potassium