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Effects of mitochondrial ATP-sensitive potassium channel opener and hypoxic preconditioning on the hyperpolarization-activated current of sinoatrial node cells in neonatal rats
Authors:ZHANG Qian  SONG Zhi-yuan  TONG Shi-fei  Huang Ji
Institution:Department of Cardiology, Southwest Hospital, Third Military Medical; University, Chongqing 400038, China
Abstract:AIM: To compare the effects of hypoxic preconditioning (HP) and mitochondrial ATP-sensitive potassium (KATP) channel opener pretreatment on the hyperpolarization-activated current (If) in sinoatrial node cells.METHODS: Sinoatrial node cells were randomized to five groups: ① Control;②Hypoxia/reoxygenation (H/R);③ HP;④ Diazoxide (mitochondrial KATP channel opener)+H/R;⑤ 5-HD (mitochondrial KATP channel blocker)+HP.At the end of the experiment, If was recorded by whole-cell patch clamp technology.RESULTS: ①H/R significantly enhanced the current densities of If, shifted the current activation curve to more positive value by changing the half-activation voltage from (-98.9±2.4)mV to (-85.2±2.5) mV (P<0.01).② Both diazoxide pretreatment and HP remarkably reduced the augmented current density caused by H/R and shifted the current activation curve to more negative value by changing the half-activation voltage to (-90.7±5.0) mV (P<0.01) and (-92.2±1.9) mV (P<0.01).③ 5-HD pretreatment blocked the effects of HP and reversed the half-activation voltage to (-86.3±2.7) mV (P<0.01).CONCLUSION: The study demonstrates that both mitochondrial KATP channel opener pretreatment and HP make current density and kinetics of If to approach normal level and to maintain electrophysiological stability of sinoatrial node cells during H/R.
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