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Stimulation of Transepithelial Na+ Current by Extracellular Gd3+ in Xenopus laevis Alveolar Epithelium

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Abstract

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 (Gd3+) increased I sc in a dose-dependent manner (EC 50 = 23.5 µM). The effect of Gd3+ 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 Gd3+ on transepithelial Na+ transport. PHMB increased I sc and this stimulation was similar to the effect of Gd3+. Co-application of PHMB and Gd3+ had no additive effects on I sc. In cell-attached patches on Xenopus oocytes extracellular Gd3+ 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 Gd3+ directly modulates the activity of ENaCs.

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Acknowledgements

We thank S. Kristek, B. Kahnert and M. Buss for excellent technical assistance. The authors thank Professor B.C. Rossier for providing the Xenopus cDNA. All experiments were in agreement with the German “Laws of animal care” [permission II 25.3-19c, 20.15(1)]. The present study was supported by the Deutsche Forschungsgemeinschaft.

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  1. Institut of Animal Physiology, Justus-Liebig-University Giessen, D-35392 Giessen, Germany

    M. Fronius, W. Clauss & M. Schnizler

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Fronius, M., Clauss, W. & Schnizler, M. Stimulation of Transepithelial Na+ Current by Extracellular Gd3+ in Xenopus laevis Alveolar Epithelium . J. Membrane Biol. 195, 43–51 (2003). https://doi.org/10.1007/s00232-003-2043-7

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