Impairment of Na+ transport across frog skin by Tl+: Effects on turnover, area density and saturation kinetics of apical Na+ channels
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Na+ transport across abdominal skin of the frogs,Rana temporaria andRana esculenta was followed by measuring Na+-dependent short-circuit, current (INa) kinetics andINa fluctuations induced by triamterene, a diuretic.
Exposure of the skin to serosal Tl+ led to a pronounced and irreversible drop inINa andINa-blocker noise.
At low serosal Tl+ concentrations, we observed mainly a decrease in the apparent Michaelis constant forINa saturation while, at larger [Tl+], the maximalINa 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 singlechannel 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.
Key wordsFrog skin Na+ transport Apical membrane Noise analysis Thallium
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