LOW EXTERNAL K+ REGULATES NA,K-ATPASE ALPHA(1) AND BETA(1) GENE-EXPRESSION IN RAT CARDIAC MYOCYTES

Incubation of mammalian cells in medium containing low K+ is often associated with an increase in Na,K-ATPase activity and content. In the present studies, we investigated the effect of low K+ on the regulation of Na,K-ATPase alpha(1) and beta(1) gene expression in primary cultures of neonatal rat cardiac myocytes. Northern blot hybridization analysis indicated that exposure of cardiocytes to a medium containing 0.3 mmol/L K+ for 72 h resulted in 1.8- and 3.3-fold increases in the abundance of a, and beta 1 mRNAs, respectively, compared with control cells exposed to 5.4 mmol/L K+. To investigate the molecular mechanism of the low K effect on beta(2) mRNA content, we constructed chimeric genes with a full-length and deleted portion of the 5' end of the rat beta(1) gene linked to the firefly luciferase gene. Transient transfection experiments using these constructs indicated that beta(1) gene sequences between -102 and +151 base pairs (bp) are required for low K+-induced trans-activation of reporter gene expression. Taken together, these results indicate that low Kf induction of p, mRNA abundance in neonatal rat cardiac myocytes is mediated by regulatory DNA sequences in close proximity to the site of transcription initiation of the beta(1) gene.