Zhou Hong-Yi, Han Chong-Yang, Wang Xiao-Liang
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Sheng Li Xue Bao. 2006 Apr 25;58(2):136-40.
The Na(+)-Ca(2+) exchange is a major pathway for removal of cytosolic Ca(2+) in cardiac myocytes. To explore the effects of temperature, intracellular Na(+), ATP and pH on Na(+)-Ca(2+) exchange currents (I(Na/Ca)) of intact guinea-pig myocytes, the whole-cell patch-clamp technique was used to record I(Na/Ca) in isolated guinea-pig ventricular myocytes. We found that I(Na/Ca) at 34 degrees C was four times higher than that at 22 degrees C. However, intracellular acidification had no obvious influence on bidirectional I(Na/Ca). At 2224 degrees C , intracellular ATP depletion and intracellular acidification did not markedly affect bidirectional I(Na/Ca) either. At 3437 degrees C , intracellular ATP depletion and intracellular acidification synergistically inhibited the outward and inward currents of I(Na/Ca), and blocked the inward currents of I(Na/Ca)more potently than the outward currents of I(Na/Ca). The effect of ATP on I(Na/Ca) is temperature-dependent. Intracellular higher sodium increased the outward currents of I(Na/Ca) however it did not increase, even sometimes decreased the inward currents of I(Na/Ca). These results suggest that intracellular ATP depletion and intracellular acidification synergistically impair Ca(2+) extrusion via forward mode Na(+)-Ca(2+) exchange, and intracellular sodium overload increases Ca(2+) influx via reverse mode Na(+)-Ca(2+) exchange, leading to calcium overload respectively.
钠钙交换是心肌细胞中清除胞质钙的主要途径。为了探究温度、细胞内钠、三磷酸腺苷(ATP)和pH值对完整豚鼠心肌细胞钠钙交换电流(I(Na/Ca))的影响,采用全细胞膜片钳技术记录分离的豚鼠心室肌细胞中的I(Na/Ca)。我们发现,34℃时的I(Na/Ca)比22℃时高四倍。然而,细胞内酸化对双向I(Na/Ca)没有明显影响。在2224℃时,细胞内ATP耗竭和细胞内酸化对双向I(Na/Ca)也没有显著影响。在3437℃时,细胞内ATP耗竭和细胞内酸化协同抑制I(Na/Ca)的外向电流和内向电流,并且对I(Na/Ca)内向电流的阻断作用比对I(Na/Ca)外向电流的阻断作用更强。ATP对I(Na/Ca)的影响具有温度依赖性。细胞内较高的钠浓度增加了I(Na/Ca)的外向电流,然而它并没有增加,甚至有时会降低I(Na/Ca)的内向电流。这些结果表明,细胞内ATP耗竭和细胞内酸化协同损害通过正向模式钠钙交换的钙外排,细胞内钠超载通过反向模式钠钙交换增加钙内流,分别导致钙超载。