Hershman K M, Levitan E S
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Am J Physiol. 1998 Dec;275(6):C1473-80. doi: 10.1152/ajpcell.1998.275.6.C1473.
Regulation of voltage-gated K+ channel genes represents an important mechanism for modulating cardiac excitability. Here we demonstrate that expression of two K+ channel mRNAs is reciprocally controlled by cell-cell interactions between adult cardiac myocytes. It is shown that culturing acutely dissociated rat ventricular myocytes for 3 h results in a dramatic downregulation of Kv1.5 mRNA and a modest upregulation of Kv4.2 mRNA. These effects are specific, because similar changes are not detected with other channel mRNAs. Increasing myocyte density promotes maintenance of Kv1.5 gene expression, whereas Kv4.2 mRNA expression was found to be inversely proportional to cell density. Conditioned culture medium did not mimic the effects of high cell density. However, paraformaldehyde-fixed myocytes were comparable to live cells in their ability to influence K+ channel message levels. Thus the reciprocal effects of cell density on the expression of Kv1.5 and Kv4.2 genes are mediated by direct contact between adult cardiac myocytes. These findings reveal for the first time that cardiac myocyte gene expression is influenced by signaling induced by cell-cell contact.
电压门控钾通道基因的调控是调节心脏兴奋性的重要机制。在此我们证明，两种钾通道mRNA的表达受成年心肌细胞间细胞-细胞相互作用的反向调控。结果显示，将急性分离的大鼠心室肌细胞培养3小时会导致Kv1.5 mRNA显著下调，Kv4.2 mRNA适度上调。这些效应具有特异性，因为其他通道mRNA未检测到类似变化。增加心肌细胞密度可促进Kv1.5基因表达的维持，而Kv4.2 mRNA表达与细胞密度呈反比。条件培养基不能模拟高细胞密度的作用。然而，多聚甲醛固定的心肌细胞在影响钾通道信息水平的能力上与活细胞相当。因此，细胞密度对Kv1.5和Kv4.2基因表达的反向作用是由成年心肌细胞间的直接接触介导的。这些发现首次揭示心肌细胞基因表达受细胞-细胞接触诱导的信号传导影响。
