Effects of cadmium on Na+ transport in the isolated skin of the toad Pleurodema thaul

Cadmium ions applied to either (outer or inner) surface of the isolated toad skin dose-dependently increased the short-circuit current (SCC), the potential difference (V) and the active sodium conductance (GNa) in the concentration range 0.07–0.50 mM. Maximal stimulatory effect was over 30% with an EC50 of about 0.1 mM. The effect of the highest concentration used (0.75 mM) decreased considerably, and when it was applied to the inner surface (10 experiments), induced between 30% and 40% inhibition of the electric parameters in four experiments. Pretreatment with amiloride inverted the stimulatory effect of externally applied Cd2+, suggesting competitive action on the apical Na+ channel. The effect of noradrenaline (NA) was increased after outer application of Cd2+ and decreased after inner application of the metal: the latter effect might be due to cadmium inhibition of the activity of Na+,K+-ATPase. On the other hand, pretreatment with amiloride was followed by partial although transient reversal of its effects by serosal Cd2+, which might be explained by action of cadmium on cytoplasmic lysine residues concerned with Na+ channel gating. The amiloride test showed that the increment of the electric parameters was due principally to stimulation of the driving potential for Na+ (V-ENa+) and that inhibition was accompanied by a reduction in the V-ENa+ and by a significant decrease in skin resistance indicating possible disruption of membrane or cell integrity. These data are in favor of the possibility that externally applied Cd2+ activates toad skin ion transport, partly by increasing apical sodium conductance and also by stimulating the V-ENa+, and that internally applied Cd2+, with easier access to membrane and cellular constituents, may inhibit the sodium pump.