Xie Z, Liu J, Malhotra D, Sheridan T, Periyasamy S M, Shapiro J I
The Departments of Medicine and Pharmacology Medical College of Ohio, Toledo 43614-5089, USA.
Ren Fail. 2000;22(5):561-72. doi: 10.1081/jdi-100100897.
In neonatal myocytes grown in culture, reductions in extracellular potassium concentration produced a hypertrophic response as assessed by induction of early response genes, atrial natriuretic peptide and skeletal actin, and repression of the alpha3 isoform of the sodium pump in a dose dependent manner. The degree of alpha3 repression appeared to be dose dependent with decreases in media (K). Similarly, decreases in media potassium concentrations caused increases in cytosolic calcium concentration in a dose dependent manner; moreover these increases in cytosolic calcium concentration correlated quite well with repression of alpha3 expression. In contrast, although moderate reductions of potassium concentration induced upregulation of skACT and ANP, severely reduced potassium concentrations caused repression of skACT and ANP expression. In parallel studies performed in vivo, 3-5 weeks dietary K restriction induced molecular phenotypical changes similar to that seen in the neonatal myocyte model without demonstrable growth as assessed by the heart weight/body weight ratio. However, when rates subjected to dietary K restriction were subsequently subjected to acute aortic constriction, cardiac growth was greater than in rats fed a control diet. These data suggest that hypokalemia may produce molecular phenotypic alterations consistent with cardiac hypertrophy as well as contribute to hypertrophy in an in vivo model.
在体外培养的新生心肌细胞中，细胞外钾离子浓度降低会产生肥厚反应，这可通过早期反应基因、心房利钠肽和骨骼肌肌动蛋白的诱导以及钠泵α3亚型的剂量依赖性抑制来评估。α3抑制程度似乎与培养基（钾）浓度降低呈剂量依赖性。同样，培养基钾离子浓度降低会以剂量依赖性方式导致细胞质钙浓度升高；此外，这些细胞质钙浓度的升高与α3表达的抑制密切相关。相比之下，虽然适度降低钾浓度会诱导skACT和ANP上调，但严重降低钾浓度会导致skACT和ANP表达受到抑制。在体内进行的平行研究中，3 - 5周的饮食钾限制诱导了分子表型变化，类似于新生心肌细胞模型中所见，通过心脏重量/体重比评估无明显生长。然而，当接受饮食钾限制的大鼠随后接受急性主动脉缩窄时，心脏生长大于喂食对照饮食的大鼠。这些数据表明，低钾血症可能产生与心肌肥厚一致的分子表型改变，并在体内模型中促进肥厚。
