title: Unanticipated lessening of the rise in extracellular potassium during ischemia by pinacidil.
abstract: BACKGROUND
  The efflux of potassium (K) through the ATP-sensitive K channel is considered an important cause of the rise in extracellular K ([K+]e) during no-flow ischemia. We postulated that agents that enhance K conductance in this channel would enhance the rise in [K+]e.
  
  
  RESULTS
  We studied the effects of 10 and 25 mumol/L pinacidil, and ATP-sensitive K channel opener that provides metabolic protection to the ischemic myocardium, on the rise in [K+]e recorded by K-sensitive electrodes, the change in action potential duration (APD) recorded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular septa. Pinacidil 25 mumol/L unexpectedly lessened the rise in [K+]e and the activation delay in both preparations. Pinacidil 10 mumol/L had no effect in the rabbit and only a slight effect in the pig. Both concentrations significantly exaggerated the APD shortening induced by ischemia. By varying stimulation frequency, we demonstrated that the rise in [K+]e during ischemia, both before and after pinacidil, correlated with the time that the action potential was at its plateau voltage.
  
  
  CONCLUSIONS
  Our results indicate that the rise in [K+]e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K+]e by pinacidil reflects the balance of its effects on these several parameters.
authors.affiliation: Department of medicine, University of North Carolina at Chapel Hill, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kanda
authors.forename: I
authors.initials: I
authors.lastname: Watanabe
authors.forename: M L
authors.initials: ML
authors.lastname: Williams
authors.forename: C L
authors.initials: CL
authors.lastname: Engle
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: G G
authors.initials: GG
authors.lastname: Koch
authors.forename: L S
authors.initials: LS
authors.lastname: Gettes
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D015425:Myocardial Reperfusion; D020110:Pinacidil; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D011188:Potassium