缺血/再灌注对心室肌细胞膜离子通道的影响

缺血心肌获得再灌注后心律失常发生率理应下降，但反见增多，长期令人费解。以酶解豚鼠心室肌细胞为研究对象，应用膜片钳全细胞记录方法，在模拟缺血／再灌注环境下，观察钠、钙内向电流（INa、ICa-L）、背景外向钾电流（IK1）、延迟整流钾电流（IK）和ATP敏感钾电流（IkATP）的变化，探讨再灌注心律失常的可能机制。结果表明：①模拟缺血10，20min，INa峰值电流由对照3．19±0．50nA分别下降至3．13±0．48，2．73±0．37nA（后者P＜0．05），继之再灌注10，20min，INa分别降至2．44±0．39，2．06±0．38nA（P均＜0，01）。②模拟缺血10，20minICa-L分别比对照增加11．88％，15．45％，继之再灌注10，20min，ICa-L分别增加为22．62％，22．34％。③模拟缺血5min后IK1的内向整流作用减弱，IK1电流加大，且在再灌注后并不恢复。④模拟缺血5min后IKATP即由对照的0．25±0．07nA上升为0．61±0．13nA（P＜0．01），再灌注20mini。IKARP继续增加为0．96±0．15nA（P＜0．01）。可见缺血所造成的INa下降和ICa-L上升，在再灌注后INa进一步下降，钙内流进一步增加，IK1在再灌注后也不恢复，提示缺血所造成的膜通道损伤并不因再灌注后恢复，反表现进一步的受损，对此产生的电生理异常，可能有助于诱发再灌注心

Effect of Ischemia/Reperfusion on Membrane Ionic Channels of Guinea Pig Ventricular Myocytes

Resently, the mechanism of the arrthymias increased after reperfusion in ischemia cardiac myocytes is unclear. To study the membrane ionic current mechanism of arrthymias resulted from ischemia/reperfusion, the cardiac inward sodium current (INa),L-type calcium current (ICa-L),outward background rectifier potassium current (IK1),delayed rectifier potassium current (IK) and ATP sensitive potassium current (IK.ATP) were investigated using the whole-cell patch-clamp method in single myocyte enzymatically isolated from guinea pig ventricle. The results showed that: ①the maximal peak INa decaeased from 3. 19 ±0. 50 nA in control to 3. 13± 0. 48 nA and 0. 73±0. 37nA in ischemia 10 min and 20 min respectively (later P＜0. 05). In 10 min and 20 min after reperfusion,INa further decreased to 2. 44±0. 39 nA and 2. 06±0. 38 nA in 10 min and 20 min respectively (all P＜0. 01);②the maximal　peak ICa-L increased to 11. 8% and 15. 45 % of the control in ischemia 10 min and 20 min respectively. In 10 min and 2o min after reperfusion,ICa- L further increased to 22. 62% and 22. 34% of the control;③after 5 min of ischemia IK1 was increased,the inward rectifier characteristics of IK1 was weak. The Changes of IK1 couldn't be restored after reperfusion; ④IK1 was increased after 5 min of ischemia,but it was recovered in 10 min after reperfusion;⑤IK ATP inceased from 0. 25±0. 07 nA in control to 0. 61±0. 13 nA in 5 min of ischemia (P＜0. 01 ) and increased to 0. 96±0. 15 nA in 20 min after reperfusion (P＜0. 01). The results suggest that the demages of the membrane ionic channel caused by ischemia continued even after reperfusion.The electrophysiologic abnormlity resulted from its corresponding changes of membrane ionic current during is chemia /reperfusion. A further increase of IK. ATP during reperfusion is beneficial to membrane and generates anti-ischemic and preconditioning effect.