Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Manitoba, Canada.
Mol Cell Biochem. 2004 Aug;263(1):151-62. doi: 10.1023/B:MCBI.0000041857.86178.f6.
Although low Na(+) is known to increase the intracellular Ca(2+) concentration ([Ca(2+)]i) in cardiac muscle, the exact mechanisms of low Na(+)-induced increases in [Ca(2+)]i are not completely defined. To gain information in this regard, we examined the effects of low Na(+) (35 mM) on freshly isolated cardiomyocytes from rat heart in the absence and presence of different interventions. The [Ca(2+)]i in cardiomyocytes was measured fluorometrically with Fura-2 AM. Following a 10 min incubation, the low Na(+)-induced increase in [Ca(2+)]i was only observed in cardiomyocytes depolarized with 30 mM KCl, but not in quiescent cardiomyocytes. In contrast, low Na(+) did not alter the ATP-induced increase in [Ca(2+)]i in the cardiomyocytes. This increase in [Ca(2+)]i due to low Na(+) and elevated KCl was dependent on the extracellular concentration of Ca(2+) (0.25-2.0 mM). The L-type Ca(2+)-channel blockers, verapamil and diltiazem, at low concentrations (1 μM) depressed the low Na(+), KCl-induced increase in [Ca(2+)]i without significantly affecting the response to low Na(+) alone. The low Na(+), high KCl-induced increase in [Ca(2+)]i was attenuated by treatments of cardiomyocytes with high concentrations of both verapamil (5 and 10 μM), and diltiazem (5 and 10 μM) as well as with amiloride (5-20 μM), nickel (1.25-5.0 mM), cyclopiazonic acid (25 and 50 μM) and thapsigargin (10 and 20 μM). On the other hand, this response was augmented by ouabain (1 and 2 mM) and unaltered by 5-(N-methyl-N-isobutyl) amiloride (5 and 10 μM). These data suggest that in addition to the sarcolemmal Na(+)-Ca(2+) exchanger, both sarcolemmal Na(+)-K(+)ATPase, as well as the sarcoplasmic reticulum Ca(2+)-pump play prominent roles in the low Na(+)-induced increase in [Ca(2+)]i. (Mol Cell Biochem 263: 151-162, 2004).
虽然低钠（Na+）会增加心肌细胞内的钙离子浓度（[Ca2+]i），但低钠诱导的[Ca2+]i 增加的确切机制尚未完全确定。为了在这方面获得信息，我们在不存在和存在不同干预措施的情况下，检查了低钠（35 mM）对来自大鼠心脏的新鲜分离的心肌细胞的影响。用 Fura-2 AM 荧光法测量心肌细胞中的[Ca2+]i。孵育 10 分钟后，仅在使用 30 mM KCl 去极化的心肌细胞中观察到低钠诱导的[Ca2+]i 增加，而在静止的心肌细胞中则没有。相比之下，低钠不会改变心肌细胞中 ATP 诱导的[Ca2+]i 增加。这种由于低钠和升高的 KCl 引起的[Ca2+]i 增加依赖于细胞外 Ca2+浓度（0.25-2.0 mM）。低浓度（1 μM）的 L 型钙（Ca2+）通道阻滞剂维拉帕米和地尔硫卓抑制低钠、KCl 诱导的[Ca2+]i 增加，而对单独低钠的反应无明显影响。用高浓度维拉帕米（5 和 10 μM）、地尔硫卓（5 和 10 μM）以及氨氯地平（5-20 μM）、镍（1.25-5.0 mM）、环匹阿尼酸（25 和 50 μM）和他普噻庚（10 和 20 μM）处理心肌细胞，可减轻低钠、高 KCl 诱导的[Ca2+]i 增加。另一方面，这种反应被哇巴因（1 和 2 mM）增强，而 5-（N-甲基-N-异丁基）氨氯地平（5 和 10 μM）则没有改变。这些数据表明，除了肌浆网 Na+-Ca2+交换器外，肌浆网 Na+-K+-ATP 酶以及肌浆网 Ca2+泵在低钠诱导的[Ca2+]i 增加中也起着重要作用。（Mol Cell Biochem 263: 151-162, 2004）。
