Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy.
Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy.
复制标题
DOI：
10.1172/jci116751
复制
发表时间：
1993-10
期刊：
影响因子：
--
通讯作者：
Hiroaki Matsubara;Junichi Suzuki;M. Inada
中科院分区：
文献类型：
--
作者：
Hiroaki Matsubara;Junichi Suzuki;M. Inada
多个K+通道对于神经元和心脏细胞中动作电位的复极和构型至关重要。在这项研究中，我们报告了快速失活的Shaker Kv1.4通道转录在大鼠心脏的调节机制。定量PCR分析表明，高浓度的KCl，BAY-K 8644，或12-O-十四烷酰基佛波醇-13-乙酸酯的刺激导致在一个即时的和实质性的增加（2 - 3倍）的Kv1.4 mRNA水平在自发跳动的心肌细胞从新生大鼠心室。心室Kv1.4 mRNA在出生后保持稳定水平，并随着成熟而逐渐下降。这些结果表明，Kv1.4 mRNA水平不是静态的，并通过激活细胞内信号的多种因素进行动态调节。此外，Kv1.4以及延迟整流Shaker K+通道Kv1.5 mRNA的表达模式在肥大心室中进行了检查，其中动作电位的平台期显著延长。Kv1.5 mRNA水平显著降低，而Kv1.4 mRNA水平显著升高。这种差异性调节被肥厚正常化完全逆转，表明K+通道基因调节的病理改变可能参与肥厚心脏室性心律失常的发生。
The multiple K+ channels are crucial for repolarization and configuration of the action potential in the neuronal and cardiac cells. In this study, we report the regulatory mechanisms of rapidly inactivating Shaker Kv1.4 channel transcript in the rat heart. Quantitative PCR analysis showed that stimulation with high concentration of KCl, BAY-K 8644, or 12-O-tetradecanoyl phorbol-13-acetate resulted in an immediate and substantial increase (two- to threefold) of Kv1.4 mRNA levels in spontaneously beating myocytes prepared from neonatal rat ventricles. The Kv1.4 mRNA in the ventricle remains at a steady state level after birth and gradually declines with maturation. These results suggest that the Kv1.4 mRNA level is not static and undergoes dynamic modulation by multiple factors that activate intracellular signals. In addition, the expression patterns of Kv1.4 as well as the delayed rectifier Shaker K+ channel Kv1.5 mRNAs were examined in hypertrophied ventricles in which a plateau phase of action potential is remarkably prolonged. The Kv1.5 mRNA level was dramatically repressed while the Kv1.4 mRNA level was remarkably increased. This differential regulation was completely reversed by the normalization of hypertrophy, suggesting that the pathological alterations of K+ channel gene regulation may be involved in the occurrence of ventricular arrhythmias in hypertrophic hearts.