title: Activation of glibenclamide-sensitive ATP-sensitive K+ channels during β-adrenergically induced metabolic stress produces a substrate for atrial tachyarrhythmia.
abstract: BACKGROUND
  Cardiac ATP-sensitive K(+) channels have been suggested to contribute to the adaptive physiological response to metabolic challenge after β-adrenoceptor stimulation. However, an increased atrial K(+)-conductance might be expected to be proarrhythmic. We investigated the effect of ATP-sensitive K(+) channel blockade on the electrophysiological responses to β-adrenoceptor-induced metabolic challenge in intact atria.
  
  
  RESULTS
  Atrial electrograms were recorded from the left atrial epicardial surface of Langendorff-perfused rat hearts using a 5×5 electrode array. Atrial effective refractory period and conduction velocity were measured using an S(1)-S(2) protocol. The proportion of hearts in which atrial tachyarrhythmia was produced by burst-pacing was used as an index of atrial tachyarrhythmia-inducibility. Atrial nucleotide concentrations were measured by high performance liquid chromatography. Perfusion with ≥10(-9) mol/L of the β-adrenoceptor agonist, isoproterenol (ISO), resulted in a concentration-dependent reduction of atrial effective refractory period and conduction velocity. The ISO-induced changes produced a proarrhythmic substrate such that atrial tachyarrhythmia could be induced by burst-pacing. Atrial [ATP] was significantly reduced by ISO (10(-6) mol/L). Perfusion with either of the ATP-sensitive K(+) channel blockers, glibenclamide (10(-5) mol/L) or tolbutamide (10(-3) mol/L), in the absence of ISO had no effect on basal atrial electrophysiology. On the other hand, the proarrhythmic substrate induced by 10(-6) mol/L ISO was abolished by either of the sulfonylureas, which prevented induction of atrial tachyarrhythmia.
  
  
  CONCLUSIONS
  Atrial ATP-sensitive K(+) channels activate in response to β-adrenergic metabolic stress in Langendorff-perfused rat hearts, resulting in a proarrhythmic substrate.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju-City, South Korea.
authors.forename: Shang-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Haifei
authors.initials: H
authors.lastname: Zhang
authors.forename: Igor
authors.initials: I
authors.lastname: Khaliulin
authors.forename: Stéphanie C M
authors.initials: SC
authors.lastname: Choisy
authors.forename: Richard
authors.initials: R
authors.lastname: Bond
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.forename: Said
authors.initials: S
authors.lastname: El Haou
authors.forename: James T
authors.initials: JT
authors.lastname: Milnes
authors.forename: Jules C
authors.initials: JC
authors.lastname: Hancox
authors.forename: M Saadeh
authors.initials: MS
authors.lastname: Suleiman
authors.forename: Andrew F
authors.initials: AF
authors.lastname: James
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D005905:Glyburide / Q000494:pharmacology*; D006325:Heart Atria / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology; D013610:Tachycardia / Q000503:physiopathology*; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D054086:KATP Channels; D026902:Potassium Channel Blockers; D014044:Tolbutamide; D007545:Isoproterenol; D005905:Glyburide