The Effects Of Inward Rectify Potassium Channel In Protection Of Myocardial Ischemia Postconditioning

Part1:The Effect of Inward Rectifier Potassium Channel in Ischemia Postconditioning of Isolated Rat HeartBackground:Numerous studies discovered that inward rectifier potassium channel is changed in ischemia-reperfusion injury,but its effect on myocardial ischemia postconditioning is unclear. The objective of this study is to observe the effect of inward rectifier potassium channels in the protection of myocardial ischemia postconditioning against the ischemia reperfusion injury.Method:32isolated rat hearts (n=8) suffered a45min sustained ischemia,followed by the process of sustained reperfusion (I/R group), ischemic postconditioning (IPO group), ischemic postconditioning+inward rectifier potassium channel antagonist20μmol/L BaCl2(PB group), and post-processing+inward rectifier potassium channel agonist1u mol/L Zacopride (PZ group). Recorded the hear rate(HR), left ventricular developed pressure(LVDP),±dp/dtmax,coronary flow(CF),cardiac troponin I(cTnI), malondialdehyde(MDA)and total superoxide dismutase(T-SOD), myocardial infarct size.Results:PZ group had better performance in cardiac function and coronary flow than IPO group had after the reperfusion,PZ group also reduced the release of cTnI,MDA and increased the synthesis of T-SOD. The infarct size was significantly reduced in PZ group than in IPO group (18.5±5.2%vs29.0±4.2%, P<0.05). PB group were declined in the performance of cardiac function and CF,increased in the release of cTnI,MDA, but T-SOD synthesis was decreased comparing with the IPO group.Conclusion:20μmol/L Bacl2partly eliminated,but1u mol/L Zacopride enhanced the protection of ischemia postconditioing against the myocardial ischemia reperfusion injury. Part2:The electrophysiological changes of Inward Rectifier Potassium Channel in Ischemia Postconditioning of CardiomyocyteBackground:Previous study suggested that adjusting the inward rectifier potassium channel in the process of ischemia postconditioing can affect the result of the myocardial protection against the ischemia reperfusion injury, but it is unclear the extent of change of the current density in the myocardial ischemia postconditioning. We observed the difference of inward rectifier potassium channel currents density between the groups with different procedure after a45min sustained hypoxia in cultured myocytes of neonatal rat in order to reveal its role in the postconditioning.Method:A105min continuous oxygenation(CON group),45min sustained hypoxia,proceeded with60min reoxygenation (I/R group),45min sustained hypoxia,proceeded with3×5min hypoxia/reoxyenation (IPO group) and after45min sustained hypoxia, added1μmol/L zacopride at the onset of reoxygenation (PZ group) on cultured neonatal rat myocardial cells. Patch clamp recorded the inward rectifier potassium channel current density, cell death rate was observed by using typan blue staining.Results:Compared to the I/R group, inward and outward current density of the inward rectifier potassium channel in IPO group and PZ group were significantly increased(at-120mV-22.34±3.14,-16.67±4.27vs-10.34±0.82pA/pF, P <0.05,at-10mV2.35±0.18,2.48±0.11vs0.41±0.29pA/pF, P<0.05). The myocytes mortality of IPO group and PZ group was significantly lower than that of the I/R group (49±7%,53±6%vs69±5%pA/pF, P<0.05).Conclusion:Hypoxia postconditioning increased inward rectifier potassium channel current density which may be an important mechanism to against the hypoxia-reperfusion injury by myocardial hypoxia postconditioning.