线粒体KATP通道开放剂与缺氧预适应对乳鼠窦房结细胞起搏离子流作用的比较

目的： 通过比较线粒体K_ATP通道开放剂及缺氧预适应（HP）对缺氧/复氧（H/R）乳鼠窦房结细胞起搏离子流（I_f）的作用，探讨HP对H/R时窦房结细胞电生理活动的保护机制。 方法： 取培养 2 d 的乳鼠窦房结细胞，随机分为①对照组；②H/R组；③HP组；④ diazoxide（线粒体KATP通道开放剂）+H/R组；⑤5-HD（线粒体K_ATP通道阻断剂）+HP组。以全细胞膜片钳技术检测I_f。 结果： ①H/R组各指令电压下的If密度显著高于对照组，激活曲线右移，半数最大激活电压由(-98.9±2.4)mV变为(-85.1±2.5)mV(P＜0.01)；②HP及diazoxide预处理能显著抑制I/R后升高的I_f密度，使激活曲线左移，半数最大激活电压分别为(-90.7±5.0)mV(P＜0.01)及(-92.2±1.9)mV(P＜0.01)；③5-HD预处理阻断HP效应，使I_f密度增加并使激活曲线右移，半数最大激活电压为(-86.3±2.7)mV(P＜0.01)。 结论： 线粒体K_ATP通道开放剂预处理能模拟HP效应，对抗H/R对乳鼠窦房结细胞I_f 的影响，有助于维护H/R时窦房结细胞电生理活动的相对稳定性。

Effects of mitochondrial ATP-sensitive potassium channel opener and hypoxic preconditioning on the hyperpolarization-activated current of sinoatrial node cells in neonatal rats

AIM: To compare the effects of hypoxic preconditioning (HP) and mitochondrial ATP-sensitive potassium (K_ATP) channel opener pretreatment on the hyperpolarization-activated current (I_f) in sinoatrial node cells.METHODS: Sinoatrial node cells were randomized to five groups: ① Control;②Hypoxia/reoxygenation (H/R);③ HP;④ Diazoxide (mitochondrial K_ATP channel opener)+H/R;⑤ 5-HD (mitochondrial K_ATP channel blocker)+HP.At the end of the experiment, I_f was recorded by whole-cell patch clamp technology.RESULTS: ①H/R significantly enhanced the current densities of I_f, 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 K_ATP channel opener pretreatment and HP make current density and kinetics of I_f to approach normal level and to maintain electrophysiological stability of sinoatrial node cells during H/R.