Hepatic uptake of 3,5,3'-triiodothyronine: electrochemical driving forces

We used the multiple indicator dilution technique to assess the electrochemical forces driving uptake of 3,5,3'-triiodo-L-thyronine (T3) across the basolateral plasma membrane in the single-pass perfused rat liver. With the use of 4 g/dl albumin solutions, the influx and efflux clearances were 0.020 +/- 0.005 and 0.0049 +/- 0.0017 (SE) ml.s-1.g liver-1, respectively, indicating that the total T3 concentration at equilibrium should be about four times greater in cytoplasm than in plasma. However, when the influx and efflux clearances were divided by the unbound (free) T3 concentration in the perfusate and cytosol, they were not different (3.76 +/- 0.26 vs. 4.30 +/- 0.38 ml.s-1.g liver-1), indicating that the uptake process does not generate a gradient of unbound T3 across the plasma membrane. To further test whether T3 uptake is driven by the electrical potential difference across the plasma membrane, liver cells were depolarized by isosmotic replacement of perfusate chloride with gluconate. There was no effect on uptake or efflux. To test whether uptake is coupled to influx of sodium, perfusate sodium was replaced with choline. Although there was a modest decline in both the influx and efflux clearances, there was no change in their ratio, as would be expected for sodium-coupled active transport. These results indicate that uptake of T3 across the basolateral hepatocyte membrane occurs by passive diffusion. We found no evidence to support concentrative, active transport by either electrogenic or sodium-coupled mechanisms.