Abstract
Movement of lithium both into and out of cultured rabbit lenses occurs by processes that obey Michaelis-Menten kinetics as well as by a nonsaturable process. The parameters describing the kinetics of transport are evaluated on the basis of a modified version of a pump-leak hypothesis that was shown previously to account for the fluxes of other, alkali metal cations. Potassium is a potent competitive inhibitor of the carrier-mediated transport of lithium into the lens. Lithium weakly inhibits the influx of potassium by a noncompetitive process. The observation that lithium is a weak inhibitor of potassium transport (Ki = 70 mM) while having a moderate affinity for its carrier (Km = 4.0 mM) suggests that more than one site may be responsible for the transport of potassium and lithium into the lens. Active transport of lithium out of the lens does not appear to involve the sodium pump, since the rate of sodium efflux is unaffected by lithium. Both influx and efflux of lithium are inhibited by ouabain (10-5 M) but not by amiloride (10-4 M) or oxytocin (20 milliunits per milliliter). Lithium displaces proportionate amounts of sodium and potassium from intracellular fluid when lenses are cultured in the presence of this cation. The nonsaturable exchange of lithium is independent of observed differences in electric potential, indicating that lithium does not permeate the lenticular membranes by simple diffusion of lithium ions, but rather as a complex with either a free anion or a carrier within the membrane. The affinity of lithium for the carrier is essentially equal to that of cesium and much lower than that for rubidium, whereas the kd of both lithium and rubidium is much higher than that for cesium. These differences indicate that a common pathway cannot be responsible for the discrimination between cations by both the pump and the leak.