REGULATION OF INTRACELLULAR CREATINE IN ERYTHROCYTES AND MYOBLASTS - INFLUENCE OF UREMIA AND INHIBITION OF NA,K-ATPASE

The regulation of intracellular creatine concentration in mammalian ce lls is poorly understood, but is thought to depend upon active sodium- linked uptake of creatine from extracellular fluid. In normal human er ythrocytes, creatine influx into washed cells was inhibited by 40 per cent in the absence of extracellular sodium. In washed cells from urae mic patients, sodium-independent creatine influx was normal, whereas t he sodium-dependent component of creatine influx was 3.3 times higher than normal, possibly reflecting the reduced mean age of uraemic eryth rocytes. In spite of this, the intracellular creatine concentration wa s no higher than normal in uraemic erythrocytes, implying that some fa ctor in uraemic plasma in vivo inhibits sodium-dependent creatine infl ux. Both in normal and uraemic erythrocytes, the creatine concentratio n was 10 times that in plasma, and the concentration in the cells show ed no detectable dependence on that in plasma, suggesting that the int racellular creatine concentration is controlled by an active saturable process. Active sodium-dependent accumulation of creatine was also de monstrated in L6 rat myoblasts and was inhibited when transport was me asured in the presence of 10(-4)M ouabain or digoxin, implying that up take was driven by the transmembrane sodium gradient. However, when cr eatine influx was measured immediately after ouabain or digoxin had be en washed away, it was higher than in control cells, suggesting that N a,K-ATPase and/or sodium-linked creatine transport are up-regulated wh en treated with inhibitors of Na,K-ATPase.