一氧化氮增加常氧和缺氧豚鼠心室肌细胞持续性钠电流  

Nitric oxide increases persistent sodium current of ventricular myocytes in guinea pig during normoxia and hypoxia

作　　者：马季骅[1] 王宪沛[1] 张培华[1] 

机构地区：[1]武汉科技大学医学院心脏电生理研究室,武汉430080

出　　处：《生理学报》2004年第5期603-608,共6页Acta Physiologica Sinica

基　　金：This work was supported by the Natural Science Foundation of Hubei Province (No.2003ABA189) and Science Foundation ofEducational Bureau of Hubei Province (No.2002A01011).

摘　　要：运用全细胞膜片钳记录缺氧条件下豚鼠心室肌持续性钠电流(INa.P)的变化及施加药物对其的影响,以探讨 INa.P 的本质及缺氧增大 INa.P 的机制。结果显示:(1)在常氧条件下,一氧化氮(NO)前体 L- 精氨酸(L-Arg)和供体硝普钠(SNP)浓度依赖性地增大INa.P; (2)INa.P 随缺氧时间延长而增大, 缺氧15 min 后施加 NO 合酶(NOS)抑制剂L- 硝基精氨酸甲酯(L-NAME), 不能使增大的INa.P 明显回复[(1.344 ±0.320) vs (1.301 ±0.317) pA/pF, P>0.05, n=5]; (3)缺氧时含L-NAME 的灌流液可使INa.P 明显减小,与单纯缺氧相比有显著差异[(0.914 ± 0.263), n=5 vs (1.344 ± 0.320) pA/pF, n=6, P<0.05], 但仍比常氧条件下增大[(0.914 ±0.263) vs (0.497 ±0.149) pA/pF, P<0.05, n=5]; (4)还原剂1,4-二硫代苏糖醇(DTT)不但可使L-Arg 及缺氧后施加SNP 增大的 INa.P 回复[(1.449 ± 0.522) vs (0.414 ± 0.067) pA/pF, P<0.01, n = 6 和(0.436 ± 0.141) vs (1.786 ± 0.636) pA/pF,P<0.01, n=5],而且使正常的 INa.P 减小[(0.396 ± 0.057) pA/pF vs (0.442 ± 0.056) pA/pF, P<0.01, n=6]。本实验结果表明缺氧可增大心室肌细胞的INa.P, 其作用机制可能是缺氧时心肌产生的NO 通过氧化细胞膜上钠通道蛋白所致,正常INa.P 的产生?Whole cell patch-clamp technique was used to record the changes of persistent sodium current (INa.P) and the effect of administered agents in ventricular myocytes of guinea pig to investigate the essence of INa.P and mechanism of increased INa.P of ventricular myocytes during hypoxia. The results showed: (1) Pro-NO L-arginine(L-Arg) and donor sodium nitroprusside (SNP) increased INa.P in a concentration- dependent manner in normoxia. (2) INa.P increased gradually with the prolongation of hypoxia time. After 15 min of hypoxia, administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, could not significantly recover the increased INa.P [(1.344 ± 320) vs (1.301 ± 0.317) pA/pF, P>0.05, n=5]; (3) During hypoxia the perfusion solution with L-NAME decreased the increased INa.P, and the difference was significant compared with pure hypoxia [(0.914 ± 0.263), n=5 vs (1.344 ± 0.320) pA/pF, P<0.05, n=6], whereas the amplitude of INa.P was still larger than that in normoxia [(0.914 ± 0.263) vs (0.497 ± 0.149) pA/pF, P<0.05, n=5]; (4) Reducing agent dithiothreitiol (DTT) not only recovered the increased INa.P by L-Arg and administered SNP after hypoxia [(1.449 ± 0.522) vs (0.414 ± 0.067) pA/pF, P<0.01, n=6 , and (1.786 ± 0.636) vs (0.436 ± 0.141) pA/pF, P<0.01, n=5, respectively], but also decreased the INa.P in normoxia [(0.442 ± 0.056) vs (0.396 ± 0.057) pA/pF, P<0.01, n=6]. Our results suggest that hypoxia increases INa.P of ventricular myocytes, which is induced by raised NO oxidating sodium channel protein in myocardial membrane during hypoxia. The activity of INa.P in normoxia is related to the oxidation state of the channel protein.

关 键 词：持续性钠电流 一氧化氮 缺氧 心肌 

分 类 号：R33[医药卫生—人体生理学]