Shapiro J I, Kennedy D J, Malhotra D, Xie M, Vetteth S
The Department of Medicine, University of Toledo College of Medicine, Toledo, Ohio 43614-5089, United States.
Cell Mol Biol (Noisy-le-grand). 2006 Dec 30;52(8):87-91.
We have previously noted that in neonatal myocytes grown in culture, reductions in extracellular K+ concentration produced a hypertrophic response as assessed by induction of early response genes, atrial natriuretic peptide and skeletal actin and repression of the alpha 3 isoform of the sodium pump in a dose dependent manner. Similarly, decreases in media K+ concentration caused increases in cytosolic calcium concentration in a dose dependent manner, which correlated with repression of alpha 3 expression. In the current study we demonstrate that decreases in media K+ concentration caused increases in cytosolic calcium concentration in isolated adult rat cardiac myocytes. These increases are potentiated by the addition of the cardiotonic steroid, ouabain and blocked by the addition of the Src kinase inhibitor Herbimycin A. In parallel studies performed in vivo, when rats subjected to dietary K+ restriction were subsequently subjected to partial (5/6th) nephrectomy for 4 weeks, cardiac growth was greater than in rats fed a control diet. These data suggest that hypokalemia may produce phenotypic alterations consistent with cardiac hypertrophy as well as potentiate the cardiovascular effects of cardiotonic steroids.
我们之前已经注意到，在培养的新生心肌细胞中，细胞外钾离子浓度降低会产生肥大反应，这通过早期反应基因、心房利钠肽和骨骼肌肌动蛋白的诱导以及钠泵α3亚型的抑制来评估，且呈剂量依赖性。同样，培养基中钾离子浓度降低会以剂量依赖性方式导致胞质钙浓度升高，这与α3表达的抑制相关。在当前研究中，我们证明培养基中钾离子浓度降低会导致成年大鼠离体心肌细胞的胞质钙浓度升高。这些升高通过添加强心甾类药物哇巴因而增强，并被添加Src激酶抑制剂赫司比霉素A所阻断。在体内进行的平行研究中，当对饮食钾限制的大鼠随后进行部分（5/6）肾切除4周时，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脏肥大一致的表型改变，并增强强心甾类药物的心血管效应。
