Golden K L, Fan Q I, Chen B, Ren J, O'Connor J, Marsh J D
Program in Molecular and Cellular Cardiology, Wayne State University, Detroit, MI 48201, USA.
J Mol Cell Cardiol. 2000 Apr;32(4):611-20. doi: 10.1006/jmcc.2000.1104.
The Na/Ca exchanger protein encoded by the NCX1 gene provides the predominant mechanism for calcium efflux during cardiac relaxation. Because beta -adrenergic stimulation increases expression of Ca(2+)channels (Ca(2+)influx) in cardiac myocytes, we tested the hypothesis that isoproterenol would concomitantly augment expression of NCX1. Four hour treatment of neonatal myocytes with isoproterenol significantly increased NCX1 gene and protein expression, and increased the rate of transcript initiation. Alpha-adrenergic stimulation significantly decreases NCX1 mRNA levels. Calcium transient measurements revealed that for cells that had been pretreated with isoproterenol there was a faster relaxation rate of the Ca(2+)transient in the presence of thapsigargin, indicating an enhanced rate of intracellular Ca(2+)removal. We conclude that effectors that increase calcium channel expression in neonatal myocytes also augments NCX1 gene and protein expression over a similar time course, and that this is due to enhanced NCX1 transcription. The regulation of expression of NCX1 by adrenergic pathways may play an important role in regulation of excitation-contraction coupling in cardiac myocytes.
由NCX1基因编码的钠钙交换蛋白是心脏舒张期钙外流的主要机制。由于β-肾上腺素能刺激会增加心肌细胞中钙通道（钙内流）的表达，我们检验了异丙肾上腺素会同时增加NCX1表达的假说。用异丙肾上腺素处理新生心肌细胞4小时，显著增加了NCX1基因和蛋白的表达，并提高了转录起始速率。α-肾上腺素能刺激显著降低NCX1 mRNA水平。钙瞬变测量显示，对于用异丙肾上腺素预处理过的细胞，在毒胡萝卜素存在的情况下，钙瞬变的舒张速率更快，表明细胞内钙清除速率增强。我们得出结论，在新生心肌细胞中增加钙通道表达的效应物在相似的时间进程中也会增加NCX1基因和蛋白的表达，这是由于NCX1转录增强所致。肾上腺素能途径对NCX1表达的调节可能在心肌细胞兴奋-收缩偶联的调节中起重要作用。
