Cation selectivity in active transport: Properties of the turtle colon in the presence of mucosal lithium

If mucosal Na is completely replaced by Li the isolated turtle colon exhibits a steady-state short-circuit current (I_sc) consistent with the transport of Li from mucosa to serosa. I_sc persists in the absence of a transmural electrochemical gradient for Li and is abolished by amiloride or ouabain. In the presence of mucosal Li the amiloridesensitive, transepithelial cation transport path can be described as a constant emf in series with a variable conductance. A comparison of equivalent circuit parameters, however, reveals that in the presence of mucosal Li the apparent emf of the cation transport path is markedly reduced, but the conductance of the active path may be greater than, equal to, or less than that observed in the presence of Na. In tissues characterized by a relatively low cellular conductance in the presence of Na, Li substitution increases the amiloridesensitive conductance, whereas, in tissues characterized by an initially high active "Na-conductance", the amiloride-sensitive conductance is reduced in the presence of Li. Thus, the approximate identity of I_sc in some tissues after cation substitution is a fortuitous consequence of an increased amiloride-sensitive conductance in the presence of mucosal Li coupled with a decreased apparent emf for Li transport. The addition of small amounts of Li to Na-containing mucosal or serosal solutions inhibits active Na transport, suggesting that Li exerts a "toxic" effect on the transport machinery apart from its ability to serve as a substitute cation. Transmural Na flux measurements reveal that, when the mucosal bathing solution contains comparable amounts of Na and Li, the net flow of Na through the active path is less than the total I_sc. The ratio of I_sc to the net Na flux approaches unity as the mucosal Li concentration approaches zero, confirming the notion that the "extra current" is carried by Li ions. The ratio of I_sc to the net Na flux is a linear function of the mucosal Li:Na concentration ratio and the slope of this relation can be interpreted to indicate that the ratio of the apparent rate coefficients for Li and Na movement through the active path is about 0.75.