NDT Advance Access originally published online on January 12, 2006
Nephrology Dialysis Transplantation 2006 21(4):869-880; doi:10.1093/ndt/gfk029
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Experimental Nephrology
A hypothesis linking sodium and lithium reabsorption in the distal nephron
1 Centre for Basic Psychiatric Research, Aarhus University Hospital, DK-8240 Risskov, Denmark and 2 Centre for Nephrology, Royal Free & University College Medical School, London, UK
Correspondence and offprint requests to: Klaus Thomsen, Dr.med.sci. Centre for Basic Psychiatric Research, Aarhus University Hospital, Skovagervej 2, DK-8240 Risskov, Denmark. Email: klt{at}psykiatri.aaa.dk
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 (FELi dist), amounts to approximately 0.97. In contrast, during severe dietary Na+ restriction, FELi dist 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 FELi dist 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, FELi dist is reduced to 0.35–0.55. The model shows that this reduction in FELi dist 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.
Keywords: amiloride; collecting duct; distal nephron; epithelial sodium channel, ENaC; lithium reabsorption; sodium reabsorption
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