Na+/Ca2+ exchanger overexpression impairs frequency- and ouabain-dependent cell shortening in adult rat cardiomyocytes
Na+/Ca2+ exchanger overexpression impairs frequency- and ouabain-dependent cell shortening in adult rat cardiomyocytes
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DOI：
10.1152/ajpheart.00397.2003
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Schwinger, RHG
中科院分区：
文献类型：
--
作者：
Bölck, B;Münch, G;Schwinger, RHG
Na+/Ca 2+交换器（NCX）可能会影响心脏功能，这取决于其在收缩-舒张周期中的主要作用模式，正向模式或反向模式。细胞内Na+浓度（[Na+]（i））和动作电位持续时间以及NCX蛋白表达水平调节NCX的作用模式。[Na+]（i）和NCX表达已被报道在人心力衰竭中增加。然而，心力衰竭中NCX表达改变的后果仍然是一个讨论的问题。我们的目的是通过腺病毒介导的基因转移来表征NCX表达对大鼠心肌细胞内Ca 2+转运的影响。通过体细胞基因转移（Ad. NCX GFP）与对照（Ad. GFP）。通过Na+梯度依赖性Ca-45（2+）-摄取测定的NCX活性显著增加。肌浆网Ca 2 +-ATP酶、受磷蛋白和钙螯合蛋白的蛋白表达不受NCX过表达的影响。在低刺激率下，Ad. NCX GFP。当刺激频率逐步提高到3.0Hz后，Ad. GFP细胞，而Ad. NCX GFP细胞。强心苷哇巴因的正性肌力作用在Ad. NCX GFP细胞，而β-肾上腺素能刺激的正性肌力作用保持不变。总之，NCX过表达导致在较高的刺激频率下以及在抑制肌膜Na+-K+-ATP酶后细胞缩短减少，即。例如，在增强的[Na+]（i）的条件下。在低刺激率，增加NCX表达增强细胞内收缩Ca 2+和收缩幅度。
The Na+/Ca2+ exchanger (NCX) may influence cardiac function depending on its predominant mode of action, forward mode or reverse mode, during the contraction-relaxation cycle. The intracellular Na+ concentration ([Na+](i)) and the duration of the action potential as well as the level of NCX protein expression regulate the mode of action of NCX. [Na+](i) and NCX expression have been reported to be increased in human heart failure. Nevertheless, the consequences of altered NCX expression in heart failure are still a matter of discussion. We aimed to characterize the influence of NCX expression on intracellular Ca2+ transport in rat cardiomyocytes by adenoviral-mediated gene transfer. A five- to ninefold ( dose dependent) overexpression of NCX protein was achieved after 48 h by somatic gene transfer (Ad. NCX. GFP) versus control (Ad. GFP). NCX activity, determined by Na+ gradient-dependent Ca-45(2+)-uptake, was significantly increased. The protein expressions of sarco(endo) plasmic reticulum Ca2+-ATPase, phospholamban, and calsequestrin were unaffected by NCX overexpression. Fractional shortening (FS) of isolated cardiomyocytes was significantly increased at low stimulation rates in Ad. NCX. GFP. After a step-wise enhancing frequency of stimulation to 3.0 Hz, FS remained unaffected in Ad. GFP cells but declined in Ad. NCX. GFP cells. The positive inotropic effect of the cardiac glycoside ouabain was less effective in Ad. NCX. GFP cells, whereas the positive inotropic effect of beta-adrenergic stimulation remained unchanged. In conclusion, NCX overexpression results in a reduced cell shortening at higher stimulation frequencies as well as after inhibition of sarcolemmal Na+-K+-ATPase, i. e., in conditions with enhanced [Na+](i). At low stimulation rates, increased NCX expression enhances both intracellular systolic Ca2+ and contraction amplitude.