title: Heterogeneity and function of K(ATP) channels in canine hearts.
abstract: BACKGROUND
  The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (K(ATP)) channels is challenged by recent reports that SUR1 is predominant in mouse atrial K(ATP) channels.
  
  
  OBJECTIVE
  To assess SUR subunit composition of K(ATP) channels and consequence of K(ATP) activation for action potential duration (APD) in dog hearts.
  
  
  METHODS
  Patch-clamp techniques were used on isolated dog cardiomyocytes to investigate K(ATP) channel properties. Dynamic current clamp, by injection of a linear K(+) conductance to simulate activation of the native current, was used to study the consequences of K(ATP) activation on APD.
  
  
  RESULTS
  Metabolic inhibitor (MI)-activated current was not significantly different from pinacidil (SUR2A-specific)-activated current, and both currents were larger than diazoxide (SUR1-specific)-activated current in both the atrium and the ventricle. Mean K(ATP) conductance (activated by MI) did not differ significantly between chambers, although, within the ventricle, both MI-induced and pinacidil-induced currents tended to decrease from the epicardium to the endocardium. Dynamic current-clamp results indicate that myocytes with longer baseline APDs are more susceptible to injected K(ATP) current, a result reproduced in silico by using a canine action potential model (Hund-Rudy) to simulate epicardial and endocardial myocytes.
  
  
  CONCLUSIONS
  Even a small fraction of K(ATP) activation significantly shortens APD in a manner that depends on existing heterogeneity in K(ATP) current and APD.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri; Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Hai Xia
authors.initials: HX
authors.lastname: Zhang
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Silva
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Lin
authors.forename: John W
authors.initials: JW
authors.lastname: Verbsky
authors.forename: Urvi S
authors.initials: US
authors.lastname: Lee
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Kanter
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Yamada
authors.forename: Richard B
authors.initials: RB
authors.lastname: Schuessler
authors.forename: Colin G
authors.initials: CG
authors.lastname: Nichols
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018929:Cell Culture Techniques; D003981:Diazoxide / Q000494:pharmacology*; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D054086:KATP Channels / Q000187:drug effects / Q000502:physiology*; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D054086:KATP Channels; D049990:Membrane Transport Modulators; D014665:Vasodilator Agents; D020110:Pinacidil; D003981:Diazoxide
keywords: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; ANOVA; AP; APD; ATP-sensitive potassium; ATP-sensitive potassium channel; Action potential duration; CL; Canine; Diazoxide; EGTA; Endo; Epi; HEPES; I(Kr); I(Ks); I(to); K(ATP); K(ATP-INJ); MI; Metabolic inhibition; Mid; Model simulation; Myocyte; Patch-clamp technique; Pinacidil; Sulfonylurea receptor; action potential; action potential duration; analysis of variance; cycle length; endocardial/endocardium; epicardial/epicardium; ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid; metabolic inhibitor; mid-myocardial/mid-myocardium; rapid delayed rectifier current; simulated ATP-sensitive potassium current; slow delayed rectifier current; transient outward current