Zinc is a voltage-dependent blocker of native and heterologously expressed epithelial Na+ channels

• DOI: 10.1007/s00424-002-0998-3
• Publication Date: 2015-11-11T20:24:02Z
• Authors: Bogdan Amuzescu; Andrei Segal; Maria-Luiza Flonta; Jeannine Simaels; Willy Van Driessche
• Keywords: 0303 health sciences; Patch-Clamp Techniques; Electric Conductivity; Epithelium; Sodium Channels; Cell Line; Membrane Potentials; Xenopus laevis; Zinc; 03 medical and health sciences; Oocytes; Animals; Kidney Tubules, Distal; Sodium Channel Blockers

Zn(2+) (1-1,000 microM) applied to the apical side of polarized A6 epithelia inhibits Na(+) transport, as reflected in short-circuit current and conductance measurements. The Menten equilibrium constant for Zn(2+) inhibition was 45 microM. Varying the apical Na(+) concentration, we determined the equilibrium constant of the short-circuit current saturation (34.9 mM) and showed that Zn(2+) inhibition is non-competitive. A similar effect was observed in Xenopus oocytes expressing alphabetagammarENaC (alpha-, beta-, and gamma-subunits of the rat epithelial Na(+) channel) in the concentration range of 1-10 microM Zn(2+), while at 100 microM Zn(2+) exerted a stimulatory effect. The analysis of the voltage dependence of the steady-state conductance revealed that the inhibitory effect of Zn(2+) was due mainly to a direct pore block and not to a change in surface potential. The equivalent gating charge of ENaC, emerging from these data, was 0.79 elementary charges, and was not influenced by Zn(2+). The stimulatory effect of high Zn(2+) concentrations could be reproduced by intra-oocyte injection of Zn(2+) (approximately 10 microM), which had no direct effect on the amiloride-sensitive conductance, but switched the effect of extracellular Zn(2+) from inhibition to activation.