title: Cardiac sodium/calcium exchanger preconditioning promotes anti-arrhythmic and cardioprotective effects through mitochondrial calcium-activated potassium channel.
abstract: BACKGROUND
  Reverse-mode of the Na(+)/Ca(2+) exchanger (NCX) stimulation provides cardioprotective effects for the ischemic/reperfused heart during ischemic preconditioning (IP). This study was designed to test the hypothesis that pretreatment with an inhibitor of cardiac delayed-rectifying K(+) channel (IKr), E4031, increases reverse-mode of NCX activity, and triggers preconditioning against infarct size (IS) and arrhythmias caused by ischemia/reperfusion injury through mitoKCa channels.
  
  
  METHODS
  In the isolated perfused rat heart, myocardial ischemia/reperfusion injury was created by occlusion of the left anterior descending coronary artery for 30 min followed by 120 min reperfusion. Two cycles of coronary occlusion for 5 min and reperfusion were performed, or pretreatment with E4031 or sevoflurane (Sevo) before the 30 min occlusion with the reversed-mode of NCX inhibitor (KB-R7943) or not.
  
  
  RESULTS
  E4031 or Sevo preconditioning not only markedly decreased IS but also reduced arrhythmias, which was significantly blunted by KB-R7943. Furthermore, these effects of E4031 preconditioning on IS and arrhythmias were abolished by inhibition of the mitoKCa channels. Similarly, pretreatment with NS1619, an opener of the mitoKCa channels, for 10 min before occlusion reduced both the infarct size and arrhythmias caused by ischemia/reperfusion. However, these effects weren't affected by blockade of the NCX with KB-R7943.
  
  
  CONCLUSIONS
  Taken together, these preliminary results conclude that pretreatment with E4031 reduces infarct size and produces anti-arrhythmic effect via stimulating the reverse-mode NCX, and that the mitoKCa channels mediate the protective effects.
authors.affiliation: Department of Physiology, The Fourth Military Medical University Xi'an 710032, China.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University Xi'an 710032, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Five-Year Medical Student of Grade 2012 in The Fourth Military Medical University Xi'an 710032, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Lai
authors.affiliation: Institute of Basic Medical Science, Xi'an Medical College Xi'an 710021, China.
authors.forename: Ling-Heng
authors.initials: LH
authors.lastname: Kong
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University Xi'an 710032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University Xi'an 710032, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Yi
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University Xi'an 710032, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University Xi'an 710032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Physiology, The Fourth Military Medical University Xi'an 710032, China.
authors.forename: Jing-Jun
authors.initials: JJ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D019194:Ischemic Preconditioning; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D024681:Potassium Channels, Calcium-Activated; D011725:Pyridines; D019831:Sodium-Calcium Exchanger; C063968:E 4031
keywords: Potassium channels; calcium; ischemic preconditioning; myocardial ischemia/reperfusion injury