Impairment of Na+ transport across frog skin by Tl+: effects on turnover, area density and saturation kinetics of apical Na+ channels.

Na+ transport across abdominal skin of the frogs, Rana temporaria and Rana esculenta was followed by measuring Na+-dependent short-circuit, current (INa) kinetics and INa fluctuations induced by triamterene, a diuretic. Exposure of the skin to serosal Tl+ led to a pronounced and irreversible drop in INa and INa-blocker noise. At low serosal Tl+ concentrations, we observed mainly a decrease in the apparent Michaelis constant for INa saturation while, at larger [Tl+], the maximal INa dropped irreversibly. Tl+ acts even when serosal Tl+ "transporters" like the Na+-K+ pump, or the K+ channel are nonfunctional. The rate constants for the triamterene/Na+ channel reaction were unchanged after Tl+ whereas the relaxation noise from channel blockage decreased in amplitude. Noise analysis in terms of a two-state blocking model suggested that Tl+ poisoning results in a small decrease in single-channel current through apical Na+ pathways, as well as in a drastic and irreversible drop in channel density. The impairment of Na+ transport by Tl+ can be attributed to the above cited concerted events at the level of the apical membrane.