Selective Inhibition of Inward Rectifier K + Channels (Kir2.1 or Kir2.2) Abolishes Protection by Ischemic Preconditioning in Rabbit Ventricular Cardiomyocytes Journal Articles uri icon

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  • Volume regulatory Cl channels are key regulators of ischemic preconditioning (IPC). Because Cl efflux must be balanced by an efflux of cations to maintain cell membrane electroneutrality during volume regulation, we hypothesize that I K1 channels may play a role in IPC. We subjected cultured cardiomyocytes to 60-minute simulated ischemia (SI) followed by 60-minute of simulated reperfusion (SR) and assessed percent cell death using trypan blue staining. Ischemic preconditioning (10-minute SI/10-minute SR) significantly ( P <0.0001) reduced the percent cell death in nontransfected cardiomyocytes [IPC CM 18.0±2.1% versus control (C CM ) 48.3±1.0%]. IPC protection was not altered by overexpression of the reporter gene (enhanced green fluorescent protein, EGFP). However, overexpression of dominant-negative Kir2.1 or Kir2.2 genes using adenoviruses (AdEGFPKir2.1DN or AdEGFPKir2.2DN) encoding the reporter gene EGFP prevented IPC protection [both IPC CM +AdEGFPKir2.1DN 45.8±2.3% (mean±SEM) and IPC CM +AdEGFPKir2.2DN 47.9±1.4% versus IPC CM ; P <0.0001] in cultured cardiomyocytes (n=8 hearts). Transfection of cardiomyocytes with AdEGFPKir2.1DN or AdEGFPKir2.2DN did not affect cell death in control (nonpreconditioned) cardiomyocytes (both C CM + AdEGFPKir2.1DN 45.8±0.7% and C CM +AdEGFPKir2.2DN 46.2±1.3% versus C CM ; not statistically significant). Similar effects were observed in both cultured (n=5 hearts) and freshly isolated (n=4 hearts) ventricular cardiomyocytes after I K1 blockade with 20 μmol/L BaCl 2 plus 1 μmol/L nifedipine (to prevent Ba 2+ uptake). Nifedipine alone neither protected against ischemic injury nor blocked IPC protection. Our findings establish that I K1 channels play an important role in IPC protection.


  • Diaz, Roberto J
  • Zobel, Carsten
  • Cheol Cho, Hee
  • Batthish, Michelle
  • Hinek, Alina
  • Backx, Peter H
  • Wilson, Gregory J

publication date

  • August 6, 2004

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