Effect of the putative Ca2+-receptor agonist Gd3+ on the active transepithelial Na+ transport in frog skin.

In this communication we show that Gd3+ acts as an activator of the apical sodium channel (ENaC) in frog skin epithelia. Application of Gd3+ to the apical solution of frog skin epithelia increased the Na+ absorption measured as the amiloride-inhibitable short-circuit current (Isc). The stimulation was dose dependent with a concentration for half-maximal stimulation (EC50) of 0.023 mM. The change in Isc was found to correlate with the net Na+ flux, confirming that Gd3+ enhances Na+ absorption. By monitoring the cellular potential (Vsc) with microelectrodes during addition of Gd3+, it was found that Vsc depolarized as Isc rose, indicating that Gd3+ affects apical Na+ permeability (PNa). This was confirmed by measuring the I/V relations of the apical membrane. In the presence of benzimidazolylguanidin (BIG), a drug known to abolish the Na+ self-inhibition, Gd3+ had no effect on Isc. The Na+ self-inhibition was investigated using fast changes of the apical Na+ concentration on K+-depolarized epithelia. BIG was found to abolish the Na+ self-inhibition and to activate the basal Na+ transport, whereas Gd3+ only activated the basal Na+ transport but had no effect on the self-inhibition. These results indicate the existence of an alternative nonhormonal mechanism to Na+ self-inhibition, via which both Gd3+ and BIG act, possibly components of the Na+ feedback inhibition system.