Structural and functional response of the isolated toad skin to mucosal lithium

Structural and functional changes induced by long-term Li-exposure of the outer surface of toad skin was studied. Electron microscopy revealed that total Na by Li replacement in the outer compartment of short-circuited toad skin promotes a conspicuous cellular damage expressed as focal swollen cells with altered intercellular spaces and nuclear morphology. Short-circuit current (SCC) decreases by about 70% over the first 60 min after 115 mmol/l Li-exposure. An amiloride sensitive transepithelial Li transport remains intact over a further 150 min despite the epithelial damage, indicating that the pathways across the apical barrier are functioning. Increase of the paracellular permeability is detected by elevation of Na-efflux. Partial 50% or 10% Na by Li replacements induce minor structural alterations and are not sufficient to trigger appreciable Na-efflux and SCC alterations. Therefore, low Li concentrations are less effective than 115 mmol/l in promoting morphofunctional responses. Although ouabain and Li reduce the SCC, ouabain does not promote structural lesions, showing that Li-inhibition of Na transport by itself is not responsible for the observed morphological alterations. In the light of this study, Li utilization as a tool to investigate transepithelial Na transport requires careful judgement.