Stimulation of transepithelial Na(+) current by extracellular Gd(3+) in Xenopus laevis alveolar epithelium.
In the present study we investigated the effect of extracellular gadolinium on amiloride-sensitive Na(+) current across Xenopus alveolar epithelium by Ussing chamber experiments and studied its direct effect on epithelial Na(+) channels with the patch-clamp method. As observed in various epithelia, the short-circuit current ( I(sc)) and the amiloride-sensitive Na(+) current ( I(ami)) across Xenopus alveolar epithelium was downregulated by high apical Na(+) concentrations. Apical application of gadolinium (Gd(3+)) increased I(sc) in a dose-dependent manner ( EC(50) = 23.5 microM). The effect of Gd(3+) was sensitive to amiloride, which indicated the amiloride-sensitive transcellular Na(+) transport to be upregulated. Benz-imidazolyl-guanidin (BIG) and p-hydroxy-mercuribenzonic-acid (PHMB) probably release apical Na(+) channels from Na(+)-dependent autoregulating mechanisms. BIG did not stimulate transepithelial Na(+) currents across Xenopus lung epithelium but, interestingly, it prevented the stimulating effect of Gd(3+) on transepithelial Na(+) transport. PHMB increased I(sc) and this stimulation was similar to the effect of Gd(3+). Co-application of PHMB and Gd(3+) had no additive effects on I(sc). In cell-attached patches on Xenopus oocytes extracellular Gd(3+) increased the open probability ( NP(o)) of Xenopus epithelial sodium channels (ENaC) from 0.72 to 1.79 and decreased the single-channel conductance from 5.5 to 4.6 pS. Our data indicate that Xenopus alveolar epithelium exhibits Na(+)-dependent non-hormonal control of transepithelial Na(+) transport and that the earth metal gadolinium interferes with these mechanisms. The patch-clamp experiments indicate that Gd(3+) directly modulates the activity of ENaCs.
D000818:Animals; D002478:Cells, Cultured; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D053503:Epithelial Sodium Channels; D005260:Female; D005682:Gadolinium / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis
D053503:Epithelial Sodium Channels; D006146:Guanidines; D006902:Hydroxymercuribenzoates; D015222:Sodium Channels; C030601:4-hydroxymercuribenzoate; C032996:2-benzimidazolylguanidine; D012964:Sodium; D005682:Gadolinium