Bollensdorff Christian, Knopp Andreas, Biskup Christoph, Zimmer Thomas, Benndorf Klaus
Institut für Physiologie, Friedrich-Schiller-Universität Jena, Teichgraben 8, D-07740 Jena, Germany.
Am J Physiol Heart Circ Physiol. 2004 Jan;286(1):H283-95. doi: 10.1152/ajpheart.00232.2003. Epub 2003 Aug 14.
During early myocardial ischemia, the myocytes are loaded with Na(+), which in turn leads to Ca(2+) overload and cell death. The pathway of the Na(+) influx has not been fully elucidated. The aim of the study was to quantify the Na(+) inward current through sarcolemmal KATP channels (IKATP,Na) in anoxic isolated cardiomyocytes at the actual reversal potential (Vrev) and to estimate the contribution of this current to the Na(+) influx in the ischemic myocardium. IKATP,Na was determined in excised single channel patches of mouse ventricular myocytes and macropatches of Xenopus laevis oocytes expressing SUR2A/Kir6.2 channels. In the presence of K+ ions, the respective permeability ratios for Na(+) to K(+) ions, PNa/PK, were close to 0.01. Only in the presence of Na(+) ions on both sides of the membrane was IKATP,Na similarly large to that calculated from the permeability ratio PNa/PK, indicative of a Na(+) influx that is largely independent of the K+ efflux at Vrev. With the use of a peak KATP channel conductance in anoxic cardiomyocytes of 410 nS, model simulations for a myocyte within the ischemic myocardium showed that the amplitude of the Na(+) influx and K(+) efflux is even larger than the respective fluxes by the Na(+) - K(+) pump and all other background fluxes. These results suggest that during early ischemia the Na(+) influx through KATP channels essentially contributes to the total Na+ influx and that it also balances the K(+) efflux through KATP channels.
在早期心肌缺血期间，心肌细胞内钠离子负荷增加，进而导致钙离子超载和细胞死亡。钠离子内流的途径尚未完全阐明。本研究的目的是在缺氧的离体心肌细胞实际反转电位（Vrev）下，量化通过肌膜ATP敏感性钾通道（IKATP,Na）的钠离子内向电流，并评估该电流对缺血心肌中钠离子内流的贡献。在表达SUR2A/Kir6.2通道的小鼠心室肌细胞的切除单通道片和非洲爪蟾卵母细胞的大膜片中测定IKATP,Na。在存在钾离子的情况下，钠离子与钾离子的相对渗透率PNa/PK接近0.01。只有当膜两侧都存在钠离子时，IKATP,Na才与根据渗透率PNa/PK计算的值相似，这表明在Vrev时，钠离子内流在很大程度上独立于钾离子外流。利用缺氧心肌细胞中ATP敏感性钾通道的峰值电导为410 nS，对缺血心肌中的心肌细胞进行模型模拟，结果显示，钠离子内流和钾离子外流的幅度甚至大于钠离子-钾离子泵和所有其他背景通量的相应通量。这些结果表明，在早期缺血期间，通过ATP敏感性钾通道的钠离子内流基本上促成了总的钠离子内流，并且它还平衡了通过ATP敏感性钾通道的钾离子外流。
