慢性间歇性低压低氧对发育大鼠心肌细胞中的L型钙通道的影响

Effect of chronic intermittent hypobaric hypoxia on L-type Ca 2+channels in cardiomyocytes of developing rats

目的探讨慢性间歇性低压低氧(chronic intermittent hypobaric hypoxia,CIHH)对发育大鼠L型钙电流(L-type calcium current,I_(CaL))的影响。方法新生雄性SD大鼠随机被分为:28 d CIHH干预组(CIHH28)、42 d CIHH干预组(CIHH42)、28 d对照实验组(CON28)和42 d对照实验组(CON42)。其中CIHH干预组分别在模拟3000 m海拔高度低压低氧的条件下(P_(B)=525 mmHg,PO_(2)=108.8 mmHg,5 h/d)(1 mmHg=0.133 kPa)干预28 d和42 d。采用全细胞膜片钳技术记录心室肌细胞中的I_(CaL)。结果CON和CIHH组心肌细胞I_(CaL)的峰值电流和电流-电压(I-V)关系曲线差异无统计学意义(P>0.05)。在模拟缺血-复灌(ischemia-reperfusion,I/R)过程中,I_(CaL)峰值降低,I-V曲线向上偏移(P<0.05),但CIHH组心肌细胞中I_(CaL)的变化明显小于CON心肌细胞(P<0.05)。CIHH组的I_(CaL)稳态激活曲线和稳态失活曲线在I/R前后均无显著性变化(P>0.05)。在I/R过程中,CON28和CON42组的I_(CaL)稳态失活曲线向左偏移(P<0.05),而CIHH28和CIHH42组心肌细胞没有变化(P>0.05)。结论CIHH可减轻缺血再灌注损伤对发育大鼠心室肌细胞I_(CaL)的影响。

Objective To investigate the effects of chronic intermittent hypobaric hypoxia(CIHH)on L-type calcium current(I_(CaL))in developing rats.Methods Newborn male SD rats were randomly divided into 28-day CIHH intervention group(CIHH28),42-day CIHH intervention group(CIHH42),28-day control group(CON28)and 42-day control group(CON42).The CIHH intervention group underwent exposure to hypobaric hypoxia at an altitude of 3000 meters for a duration of 28 days and 42 days respectively,with each session lasting 5 h per day.These conditions were characterized by a partial oxygen pressure(PO_(2))of 108.8 mmHg(1 mmHg=0.133 kPa)and a barometric pressure(P_(B))of 525 mmHg.The whole-cell patch clamp technique was employed to record the I_(CaL) in ventricular myocytes.Results No significant differences was observed in the peak current or the current-voltage(I-V)relationship curve of I_(CaL) in cardiomyocytes between the CON group and CIHH group(P>0.05).However,during simulated ischemia/reperfusion(I/R),the peak I_(CaL) was observed to be decreased,accompanied by an upward shift in the I-V relationship curve(P<0.05).But the change of I_(CaL) in cardiomyocytes was significantly smaller in CIHH group than in CON group(P<0.05).The steady-state activation and inactivation curves of I_(CaL) in the CIHH group showed no significant changes before and after I/R(P>0.05).However,during the process of I/R,the steady-state inactivation curve for I_(CaL) underwent a shift towards the left in both CON28 and CON42 groups(P<0.05),whereas no such shift was observed in cardiomyocytes of CIHH28 and CIHH42 groups(P>0.05).Conclusion CIHH can attenuate the effect of I/R injury on I_(CaL) in ventricular myocytes of developing rat.