title: Increased response to β₂-adrenoreceptor stimulation augments inhibition of IKr in heart failure ventricular myocytes.
abstract: BACKGROUND
  Increasing evidence indicates that the rapid component of delayed rectifier potassium current (I(Kr)) is modulated by α- and β-adrenergic stimulation. However, the role and mechanism regulating I(Kr) through β(2)-adrenoreceptor (β-AR) stimulation in heart failure (HF) are unclear.
  
  
  RESULTS
  In the present study, we investigated the effects of fenoterol, a highly selective β(2)-AR agonist, on I(Kr) in left ventricular myocytes obtained from control and guinea pigs with HF induced by descending aortic banding. I(Kr) was measured by using whole cell patch clamp technique. In control myocytes, superfusion of fenoterol (10 µM) caused a 17% decrease in I(Kr). In HF myocytes, the same concentration of fenoterol produced a significantly greater decrease (33%) in I(Kr). These effects were not modified by the incubation of myocytes with CGP-20712A, a β(1)-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551, a β(2)-AR antagonist. An inhibitory cAMP analog, Rp-cAMPS and PKA inhibitor significantly attenuated fenoterol-induced inhibition of I(Kr) in HF myocytes. Moreover, fenoterol markedly prolonged action potential durations at 90% (APD(90)) repolarization in HF ventricular myocytes.
  
  
  CONCLUSIONS
  The results indicate that inhibition of I(Kr) induced by β(2)-AR stimulation is increased in HF. The inhibitory effect is likely to be mediated through a cAMP/PKA pathway in HF ventricular myocytes.
authors.affiliation: Department of Cardiology, Yijishan Hospital of Wannan Medical College, Wuhu, China.
authors.forename: Hegui
authors.initials: H
authors.lastname: Wang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Hongjun
authors.initials: H
authors.lastname: Zhu
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.forename: Xiwen
authors.initials: X
authors.lastname: Zhang
authors.forename: Dongjie
authors.initials: D
authors.lastname: Xu
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
authors.forename: Jiangang
authors.initials: J
authors.lastname: Zou
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005280:Fenoterol / Q000494:pharmacology; D006168:Guinea Pigs; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D011412:Propanolamines / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D013873:Thionucleotides; D005280:Fenoterol; C016957:adenosine-3',5'-cyclic phosphorothioate; C026777:ICI 118551; C049763:CGP 20712A; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases