title: Role of ion channels in sepsis-induced atrial tachyarrhythmias in guinea pigs.
abstract: OBJECTIVE
  Supraventricular tachyarrhythmias, including atrial fibrillation, are occasionally observed in patients suffering from sepsis. Modulation of cardiac ion channel function and expression by sepsis may have a role in the genesis of tachyarrhythmias.
  
  
  METHODS
  Sepsis was induced by LPS (i.p.; 300 µg·kg(-1) ) in guinea pigs. Membrane potentials and ionic currents were measured in atrial myocytes isolated from guinea pigs 10 h after LPS, using whole cell patch-clamp methods.
  
  
  RESULTS
  In atrial cells from LPS-treated animals, action potential duration (APD) was significantly shortened. It was associated with a reduced L-type Ca(2+) current and an increased delayed rectifier K(+) current. These electrophysiological changes were eliminated when N(G) -nitro-l-arginine methyl ester (l-NAME) or S-ethylisothiourea was given together with LPS. In atrial tissues from LPS-treated animals, Ca(2+) channel subunits (Ca(v) 1.2 and Ca(v) 1.3) decreased and delayed rectifier K(+) channel subunits (K(v) 11.1 and K(v) 7.1) increased. However, L-NAME treatment did not substantially reverse such changes in atrial expression in LPS-treated animals, with the exception that K(v) 11.1 subunits returned to control levels. After LPS injection, inducible NOS in atrial tissues was up-regulated, and atrial NO production clearly increased.
  
  
  CONCLUSIONS
  In atrial myocytes from guinea pigs with sepsis, APD was significantly shortened. This may reflect nitration of the ion channels which would alter channel functions, rather than changes in atrial expression of the channels. Shortening of APD could serve as one of the mechanisms underlying atrial tachyarrhythmia in sepsis.
authors: Department of Anesthesiology, University of Toyama, Toyama, Japan. g0049eriki@yahoo.co.jp
authors: Yuta
authors: Y
authors: Aoki
authors: Noboru
authors: N
authors: Hatakeyama
authors: Seiji
authors: S
authors: Yamamoto
authors: Hiroyuki
authors: H
authors: Kinoshita
authors: Naoyuki
authors: N
authors: Matsuda
authors: Yuichi
authors: Y
authors: Hattori
authors: Mitsuaki
authors: M
authors: Yamazaki
mesh_terms: D000200:Action Potentials; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D018805:Sepsis / Q000150:complications*; D013617:Tachycardia, Supraventricular / Q000209:etiology / Q000503:physiopathology*
chemical_list: D020746:Calcium Channels, L-Type; D007473:Ion Channels; D008070:Lipopolysaccharides; D015221:Potassium Channels; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II