A hypothesis linking sodium and lithium reabsorption in the distal nephron.
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 (FE(Li dist)), amounts to approximately 0.97. In contrast, during severe dietary Na(+) restriction, FE(Li 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.


METHODS
We propose a model that incorporates this concept.


RESULTS
The model indicates that the lowering of FE(Li 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, FE(Li dist) is reduced to 0.35-0.55. The model shows that this reduction in FE(Li dist) can be explained by hyperpolarization of the apical membrane in ENaC-containing sub-segments, which is known to occur in this condition.


CONCLUSIONS
We conclude that the model may improve current understanding of both Na(+) and Li(+) handling in the distal nephron.
Thomsen
Klaus
K
Centre for Basic Psychiatric Research, Aarhus University Hospital, Skovagervej 2, DK-8240 Risskov, Denmark. klt@psykiatri.aaa.dk
Shirley
David G
DG
D000818:Animals; D006801:Humans; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000378:metabolism*; D009399:Nephrons / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D008094:Lithium; D012964:Sodium