title: Left-to-right ventricular differences in I(KATP) underlie epicardial repolarization gradient during global ischemia.
abstract: BACKGROUND
  The ionic mechanisms of electrical heterogeneity in the ischemic ventricular epicardium remain poorly understood.
  
  
  OBJECTIVE
  This study sought to test the hypothesis that the adenosine triphosphate (ATP)-activated K+ current (I(KATP)) plays an important role in mediating repolarization differences between the right ventricle (RV) and left ventricle (LV) during global ischemia.
  
  
  METHODS
  Electrical activity in Langendorff-perfused guinea pig hearts was recorded optically during control, ischemia, and reperfusion. Patch-clamp experiments were used to quantify I(KATP) density in isolated myocytes. Molecular correlates of I(KATP) (Kir6/SUR) were probed via reverse transcriptase-polymerase chain reaction. The role of I(KATP) in modulating repolarization was studied using computer simulations.
  
  
  RESULTS
  Action potential duration (APD) was similar between LV and RV in control hearts, but significantly different in global ischemia. Pretreatment of hearts with 10 μM glibenclamide (I(KATP) blocker) abolished the APD gradient during ischemia. In the absence of ischemia, pinacidil (I(KATP) opener) tended to shorten the APD more in the LV, and caused a small but significant increase in APD dispersion. In voltage clamp experiments, the density of the whole-cell current activated by pinacidil at depolarized potentials was significantly larger in LV, compared with RV epicardial myocytes. The mRNA levels of Kir6.1/Kir6.2 were significantly higher in LV compared with RV. Simulations showed that I(KATP) is the main determinant of LV-RV APD gradient, whereas cell-to-cell coupling modified the spatial distribution of this APD gradient.
  
  
  CONCLUSIONS
  I(KATP) is an important determinant of the epicardial LV-RV APD gradient during global ischemia, in part due to a higher current density and molecular expression in the LV.
authors: Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan 48108, USA. sanpandi@med.umich.edu
authors: Sandeep V
authors: SV
authors: Pandit
authors: Kuljeet
authors: K
authors: Kaur
authors: Sharon
authors: S
authors: Zlochiver
authors: Sami F
authors: SF
authors: Noujaim
authors: Philip
authors: P
authors: Furspan
authors: Sergey
authors: S
authors: Mironov
authors: Junco
authors: J
authors: Shibayama
authors: Justus
authors: J
authors: Anumonwo
authors: José
authors: J
authors: Jalife
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D018780:Body Surface Potential Mapping / Q000379:methods*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000503:physiopathology; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D011817:Rabbits
chemical_list: D054086:KATP Channels