A hypothesis linking sodium and lithium reabsorption in the distal nephron

Abstract

Background. A hypothesis is proposed linking Na+ and Li+ reabsorption in the distal nephron. The handling of these two ions in the distal nephron is related because they share the same apical membrane entry mechanism: the amiloride-sensitive Na+ channel (ENaC). However, the two ions exit the cell through different transport mechanisms: Na+ via the Na+-K+ -ATPase and Li+ via the Na+/H+ exchanger. Studies in rats have shown that under normal circumstances hardly any Li+ is reabsorbed in the distal nephron, so that the urinary excretion of Li+, expressed as a fraction of the delivery to the early distal tubule (FELidist), amounts to approximately 0.97. In contrast, during severe dietary Na+ restriction, FELidist decreases to 0.50-0.60. Our hypothesis is that the absence of distal Li+ reabsorption during intake of a normal diet can be explained by a negative driving force for Li+ entrance across the apical membrane in those segments in which ENaC is active. Method. We propose a model that incorporates this concept. Results. The model indicates that the lowering of FELidist during dietary Na+ restriction can be explained by activation of apical ENaC in extra sub-segments further downstream. In these extra sub-segments the driving force for Li+ reabsorption is positive, leading to significant Li+ reabsorption. During dietary K+ restriction, FELidist is reduced to 0.35-0.55. The model shows that this reduction in FELidist can be explained by hyperpolarization of the apical membrane in ENaC-containing sub-segments, which is known to occur in this condition. Conclusion. We conclude that the model may improve current understanding of both Na+ and Li+ handling in the distal nephron. © 2006 Oxford University Press.